1、Pharma R&D Annual Review 2022 Navigating the Landscape Discover more at: Paper2IntroductionWelcome to Pharmaprojects 2022 review of trends in pharmaceutical R&D.For 30 years now,Ive been taking an annual look at the evolution of pharma R&D,and in this article Ill examine the state of play at the sta

2、rt of 2022.Well assess industry trends by examining the pipeline by company,therapeutic area,disease,target,and drug type,using data from Pharma Intelligences Pharmaprojects,part of the Citeline suite of products,which has been tracking global drug development since 1980.This report will be followed

3、 up by our annual supplement reviewing the New Active Substance launches for the year just passed.But here,we will be packing our suitcases and heading to the airport to embark on a journey which circumnavigates the pharma world,travelling through both familiar territories and off the beaten track,t

4、o discover the direction of travel of the industry as it resets its compass following a turbulent couple of years,which have been quite a journey to say the least.Regular readers of this report(which has been running since 1993 so is presented here in its thirtieth edition)will know that in recent y

5、ears,Ive threaded a different theme through each edition,to highlight points,to draw analogies,and to add a little local colour into what could otherwise be a rather lengthy voyage through the dreary suburbs of statistics,charts,and tables.Themes selected so far have included astronomy,movies,the na

6、tural world,music,food and drink,and,last year,science fiction.Last autumn,as,in the UK at least,everything seemed to be pretty much back to normal COVID-wise,I selected travel for the theme of the 2022 report,expecting that this year would be the one in which everything returned to standard and,acc

7、ordingly,we would all jet off on multiple holidays,making up for the lack of travel opportunities we have had to endure since the start of 2020.Sadly,at the time of writing,it looks like I was a little premature,as the world is currently being engulfed by the biggest wave of disease thus far,thanks

8、to the highly infectious Omicron variant.However,Im hopeful that,by the time you read this,the wave will have largely broken,and that with most people triple-jabbed or recently infected(or,as in my case,both),the virus will have no place left to go,and we will at last be moving from the pandemic to

9、the endemic stage of this cruel disease.So,Im still optimistic that this year will be the one where foreign vacations come back with a bang.Therefore,like a good eco-tourist,Im sticking to the prescribed path.3Our modern jet-set lifestyle and the incredible interconnectedness of the contemporary wor

10、ld are often cited as major reasons why SARS-CoV-2 could spread so rapidly worldwide and is why most countries closed their borders at some point as a result,stymying many a planned fortnight in Marbella.While this is undoubtedly true,its worth noting that this isnt such a modern phenomenon as you m

11、ight think.Spanish flu managed to wreak havoc across the entire world perfectly successfully without supersonic planes crammed with holidaymakers making intercontinental trips in just a few hours.Its progress was most likely exacerbated by large-scale troop movements at the end of the First World Wa

12、r,and while these were on a minute scale compared with todays(or,more accurately,pre-2020s)level of international migration,it still managed to sweep across the globe in less than a year.Even in mediaeval times,there was sufficient global trade and travel to export a disease such as bubonic plague a

13、round the world efficiently.Of course,with the benefit of hindsight,the responses in some countries to COVID were sluggish,even to the point of a fiddling while Rome burned in some cases.But the reality is that any sufficiently infectious zoonosis,unless contained immediately at the point of origin,

14、is going to go global at a mile a minute,and this really isnt anything new.Tourism and travel for the masses though is indeed a wonder of the modern age.Until the 1960s,international trips were really only the province of the wealthy,and indeed,as a child,my family never ventured beyond the shores o

15、f the UK.My parents generation just didnt have that option,with my mum never having boarded a plane to this day,and my dad only having done so as part of his conscripted National Service to Egypt.All that changed when cheaper airline travel arrived in the seventies and going abroad for a summer holi

16、day became de rigueur.My generation(Im 57)thus have had a completely different experience of the world.According to one of those interactive maps that pops up on Facebook from time to time,Ive visited 43 countries so far,with journeys to all corners of the globe and trips to every continent(not coun

17、ting Antarctica).I feel truly fortunate to be living in an age where opportunities to experience so many far-off cultures and habitats first-hand exist for many of us.In fact,having that taken away temporarily was one of the hardest things to endure during the past two years of the pandemic.What was

18、 once a privilege now seems like a right.Ive been lucky to undertake some of that international travel as part of my job,partly because pharma is the epitome of a global industry.This may be one of the reasons why the public has traditionally regarded it with distrust(faceless multinational corporat

19、ions etc),but its also the reason why it could mobilize on such an extraordinary scale in response to COVID.One of the fascinating,previously under the radar,aspects of pharma R&D which the pandemic cast new light on was the global supply chain.It became evident that its not enough to just develop a

20、 vaccine:having all of its constituent parts for manufacturing of the vaccine antigen and its delivery vector,which in themselves,probably come from many different international sources,is just the start.You then need glass vials,cold storage,transport,needles,PPE,and trained vaccinators.Plus,you ne

21、ed infrastructure something often found wanting outside of the richer,developed countries.Getting the vaccines to people all over the world has been putting together a jigsaw where the constituent pieces are scattered across the globe.And,as has often been stated with respect to vaccination,no-one i

22、s safe until everyone is safe.The rise of Omicron is testament to that.Travel also seems like a good theme as the R&D process itself is very much like a journey.At the start of drug development,the destination must be decided on and then the logistics of the trip must be determined.Having done your

23、planning,the preclinical phase is like gathering 4everything together before embarking on your travels:getting your candidate and checking its efficacy,toxicity,and delivery is a bit like getting your passport,tickets,and foreign currency together and packing your suitcase before you leave the house

24、.Then,youre ready for take-off.After arriving at your destination,youre getting the lie of the land,working out how things work in this new territory a bit like Phase I trials.Having settled in,youre willing to become a little more adventurous,taking in the sights as you move into Phase II.And by Ph

25、ase III of your holiday,youre growing in confidence and starting to try out a few phrases in the local lingo.Reaching the filing stage,youre beginning to feel like a native and contemplating retiring to this little piece of paradise.All thats left to complete the perfect vacation is to successfully

26、launch yourself back home(no mean feat in the era of pre-departure COVID tests!).Just like a holiday of course,there are lots of things which can go wrong at any stage of pharma R&D along the way.Many compounds never make it out of preclinical,akin to being refused boarding to your plane as you forg

27、ot to renew your passport.Arriving at your destination in human studies,things dont always pan out the hotel often doesnt look like the pictures in the brochure.Even as your drug passes through the latter stages of its journey,something unexpected can go wrong you can get lost after turning off the

28、beaten track,or even have to cut your expedition short after one too many sangrias sees you spending a night in the local police cell.Modern travel,like drug development,is rarely devoid of stress,and is composed of many moving parts,which all need to align like the stars guiding an ancient mariner

29、if youre to successfully complete your voyage.As with travel,information is key if one is to effectively negotiate pharma R&D.For a vacation,you need the most up-to-date information,including timetables and maps.And you need to know how your resort has changed since your last visit.This is what this

30、 report intends to do.Using analogies from,and references to,the world of travel and tourism along the way,the Pharma R&D Report will act like the guidebook you purchase before you plan your trip the Rough Guide to Pharma R&D if you like.Well document how the land of drug development is changing,hig

31、hlight some of the local points of interest which no-one can afford to miss,and also direct you to some of the more surprising and interesting secluded out-of-the-way places which you may not have discovered without using the local knowledge of our experts.So,hitch a ride with me and strap yourself

32、in Ill be your tour guide.Its time to journey into the centre of the R&D pipeline.“A journey of athousand miles begins with a single step.”Lao Tzu5Checked-In and Ready for Take-Off:Total Pipeline SizePharma breaking the sound barrier as it zooms past 20KAs we wake up and excitedly make our departure

33、 on the first day of our trip,lets get this show on the road by taking a birds eye view of the scope of the territory well be exploring,by looking at the total number of drugs currently in the pipeline.As usual,its worth starting off with a definition of what we mean by pipeline,since all of the ana

34、lyses in this report will be focusing on this set of drugs.By pipeline,we mean that we are counting all drugs in development by pharmaceutical companies,from those at the preclinical stage,through the various stages of clinical testing and regulatory approval,and up to and including launch.Launched

35、drugs are still counted,but only if they are still in development for additional indications or markets.Drugs whose development has had the brakes put on,or whose development is complete,are not included.All data were collected on 4 January 2022.Like planning a holiday to a country with an unstable

36、regime,it hasnt been so easy to predict what we would find on landing in 2022.COVID-19 undoubtedly had a disrupting effect,coming as it did two years ago apparently from nowhere.It was certainly a case of all-hands-on-deck as pharma made a titanic effort to avoid the COVID iceberg,but did the pandem

37、ic rock the boat and cause everyone to man the lifeboats,or are we now pursuing plain sailing as we chart towards calmer waters?If youre interested in a broad-brush answer to this question,perhaps a look at the total number of drugs currently in R&D would float your boat.Well,Figure 1 appears to sho

38、w that the industry is cruising,and it is full steam ahead.Hitting 20,109 pipeline drugs,pharma appears to have the wind in its sails,if youll excuse the mildly mangled metaphor.This represents an expansion rate of 8.22%over 2021s number a growth rate coming in close to twice the 4.76%seen over the

39、previous 12 months.Its not as big as 2020s 9.62%but,given that 2019 and 2018s figures were 5.99%and 2.66%,respectively,its at the upper end of the figures seen over the past five years,and considerably above the five-year average of 6.25%.It also takes the pipeline size beyond the magical 20,000 num

40、ber for the first time.This means that there are 1,527 more drugs in development than there were this time last year,whereas last year the uplift was only of 845 drugs.As well see later,new additions of COVID-related agents came in at a much lower rate during the past 12 months,so they dont account

41、for this big increase.It seems that pharma is,however,sailing along at some speed,buoyed by the prevailing winds resulting from the crisis.In fact,6,343 new drugs were added to the Pharmaprojects database during 2021 considerably more than the 5,544 added during 2020 and leaving the 4,730 added the

42、year before that in its wake.Undoubtedly there is some effect here of better detection of new drugs thanks to our ever-improving editorial methods,but this is surely only part of the story.It really does feel this year that,rather than being hampered by the pandemic,the industry has been turbocharge

43、d by it.And this may be an underestimate of its growth rate.This time last year,around 4%of active drugs had not been updated for more than 12 months,whereas this year,we have reduced that figure down to 0.5%.The end result of the 620015,00010,00015,00020,00025,00020022003200420052006200720082009201

44、0200002020212022DRUG COUNT5,9956,1986,4166,9947,3607,4067,7379,6059,7379,71310,45210,47911,30712,30013,71814,87215,26716,18117,73718,5829,21720,109YEARFIGURE 1:Total R&D pipeline size,by year,200122review which we conduct for many drugs that havent been updated for o

45、ver a year is a move of that drug to the No Development Reported(NDR)status,thus taking it out of the Active data set.So,improved scrutiny of drugs for which little new information has been released can lead to more being marked as Inactive,thus actually lowering this years Active total.Without this

46、 improved scrutiny,we could be looking at double-digit growth for the total pipeline size.The speedboat of pharma is indeed generating considerable churn in the R&D ocean.As well as the 6.3K new drugs added,over the course of the year a total of 221 drug discontinuations were confirmed and a further

47、 4,658 were moved out of the Active data set as a result of being marked as NDR actually similar figures to those seen in 2020.Fortunately,any suppression in the overall pipeline size brought about by improved editorial practice has a systematic effect,so comparisons within each analysis will remain

48、 perfectly valid.Still,nearly six and a half thousand new R&D candidates joining the pipeline in a single year is quite extraordinary.How do these drugs break down by therapeutic area?No fewer than 38.8%of them have an anticancer focus,with neurologicals coming in second at 14.7%,and Source:Pharmapr

49、ojects,January 20227anti-infectives,where most of the COVID-related entities reside,only coming in third with 12.0%of new drugs.Interestingly,this is well below the 17.5%of new drugs which are focused on one or more rare disease of which more later.Does its rapidly expanding waistline imply that eve

50、rything is all ship shape and Bristol fashion in the world of pharma?As always,we caveat the excitement at a bigger-than-ever pipeline with the warning that the vast majority of these drugs are still prelaunch,so are costs with risks attached,rather than successful revenue-generators curing patients

51、.Has pharma followed on from a record-breaking year in 2020 when,despite the best efforts of the pandemic to derail it,it had its most successful year ever,delivering 82 New Active Substances(NASs)to the market?While well be dealing with the finalized list of 2021s drug debuts in the follow-up suppl

52、ement to this report,early indications are that it was another very successful year,with over 80 confirmed NAS launches already,and this figure is set to rise.It does indeed seem then,that the pharmaceutical industry is continuing to chart the right course through the choppy COVID-infested waters.“T

53、he world is a book and those who do not travel read only one page.”Saint Augustine8Arrival:The 2022 Pipeline by Phase Early development surges as pharma gets its place in the sunThe pharmaceutical industry,like the travel industry,is always looking for something new.Another thing they have in common

54、 is a propensity for making lists and league tables.Depending on which travel magazine or website/blog you read,the hot new tourist destinations for 2022,as travel reopens,are Greenland(and its exciting sounding Disko Bay),Rwanda,and Turkmenistan,as well as the cities of Auckland,New Zealand(which s

55、eemed to feature in a few polls);Gyeongju,South Korea;and Oslo,Norway.These all sound like intriguing and innovative destinations to me,as someone who loves to try somewhere new.Innovation and newness are also key to pharma,and perhaps unsurprisingly,the growth in the pipeline is concentrated at the

56、 more cutting-edge end of the development cycle.We can see this clearly if we break down the 20,109 drugs in the pipeline by their current global statuses the most advanced stage of development each drug has reached in any country,for any disease,and by any company.This is what Figure 2 does.You can

57、 see that the lions share of pipeline expansion occurred in drugs which were still at the preclinical stage,with a growth rate here of a phenomenal 11.0%.Remember,all of these drugs have been confirmed by our analysts to be genuine development candidates authenticated as still being taken forward wi

58、thin the past 12 months we dont just scrape the internet and add in any compound we come across.This is a considerable uptick on the rate of expansion in the preclinical pipeline witnessed in 2020,which was only 6.0%.An additional 1,128 drugs are in preclinical development compared with this time la

59、st year,although its worth noting that its at this phase that a lot of the churn noted earlier will have taken place,so there are not just more overall,but many more different ones this year compared to last.These drugs of course have a long way to go,but as the saying goes,“to travel hopefully can

60、be better than to arrive”.The number of drugs in Phase I clinical trials also seems to have stepped up a gear.With 2,947 drugs at the Phase I stage at the start of 2022,pharma has definitely been putting its foot on the gas here.This represents a growth rate of 10.1%,outpacing the overall expansion

61、in the pipeline and overtaking the 6.4%seen last year.9And whereas,at Phase II and Phase III were a paltry 2.0%and 0.9%,respectively,last year,this year pharma has been burning rubber here too,recording much more rewarding accelerations of 6.4%and 8.7%,respectively.Note that these data are a snapsho

62、t in time:the fact that there are roughly the same numbers of drugs in Phase II as there are in Phase I in no way means that virtually all drugs undergoing Phase I then progress serenely to Phase II.In fact,there is considerable attrition between the two Phases,but as Phase II development generally

63、takes much longer,drugs pile up at the Phase II stage.Its a bit like how a traffic jam builds up when the motorway goes down from three lanes to two.FIGURE 2:Pipeline by development phase,2022 versus 2021PreclinPhase IPhase IIPhase IIIPre-regRegisteredLaunchedSuspendedN/A2,0004,0006,0008,00010,000DR

64、UG COUNT676294727472922239STAGE OF DEVELOPMENT12,00020212022Source:Pharmaprojects,January 2022N/A:not applicable and is applied to companion diagnostics prelaunch10For Phase III in particular,this represents something of a recovery after pharma suffered a

65、bit of a breakdown in recent years,or at the very least was crawling along in the slow lane.This can be seen more clearly in Figure 3,which looks a little further back in time to see how trends in the numbers of drugs in clinical trials have changed over the past 15 years.You can clearly see that th

66、e numbers at Phase III have been idling in neutral in recent years,but that this year,they seem to have been hotwired into action somewhat.Similarly,its clear that pharma is flooring the gas pedal more across the other clinical stages.While the numbers of drugs in Phase I and Phase II has always inc

67、reased,the 202122 period really does see the industry tearing along in the fast lane,overtaking previous years and leaving them for dust.FIGURE 3:Clinical phase trends,200722Phase IPhase IIPhase III500DRUG COUNT1,00015002,0002,5003,0003,500200720082009200001920202021

68、2022Source:Pharmaprojects,January 202211These statistics certainly suggest that,rather than meeting its Waterloo in its battle with SARS-CoV-2,the industry was imbued with a new kind of Dunkirk spirit.The wobble in trial activity seen at the beginning of the outbreak was mercifully short-lived.In te

69、rms of industry-sponsored clinical development,in 2020 there was a 12%decrease in confirmed trial starts for diseases other than COVID-19,pushing the number of trial starts for drug development not specifically focused on vaccines or treatments for the new coronavirus back to a level last seen in 20

70、15.However,in 2021 we saw a modest 2%increase in confirmed trial starts compared to the 2020 numbers.“A recovery in trial starts is to be expected given many sponsors have now started to embrace newer ways of both recruiting for and running clinical trials,plus the wide variation in size and type of

71、 COVID-related restrictions in different regions over time”,comments Andy Benson,Senior Director of Trialtrove,our sister product which tracks individual clinical trials in the same way Pharmaprojects does drugs.“And we can expect the number of confirmed 2021 trial starts to tick up a little more,as

72、 delayed reporting of trial activity(particularly for Phase I trials and in some territories)still has an impact when analysing trial data,so that 2%increase could be a few percentage points higher when the dust settles”,he continued.It seems that those running clinical development,after sailing clo

73、se to the wind for a bit,have indeed weathered the COVID storm and are now experiencing something of a following breeze.“Ones destination is never a place,but a new way of seeing things.”Henry Miller12Meet Your Fellow Travelers:Top CompaniesFamiliar faces on the tour are joined by Chinese newcomersI

74、ts probably a clich,but travelers are often divided into two types:the adventurous and the safe.Those in the former travelers group always like to go somewhere new,enjoying nothing more than the thrill of heading off-piste,negotiating challenging terrains or unfamiliar languages,and generally pushin

75、g the envelope to get that new experience or that rarely seen vista.Then there are those who dont like to be taken too far out of their comfort zones,returning to the same familiar resort year after year,and choosing the egg and chips option from the English menu in the local taverna.I would like to

76、 think that I fit firmly into the former camp(although having said that,I have been to Ibiza 15 times!),but I can certainly understand that some have a fondness for their regular haunts and the greater chance of relaxation that familiarity brings.The latter type of tourist would certainly be feeling

77、 at home looking at this years chart of the top 25 companies by the size of their R&D pipelines(Table 1).There are no unfamiliar faces in the top 15 at all,which comprises exactly the same 15 companies as last year,with very little jostling for new positions either.Its a sixth year with the largest

78、R&D empire for Novartis,although the companys pipeline did contract slightly from 232 to 213 drugs.It also once again originated the most drugs.However,it had a slightly less successful year,only being involved in two first launches,unlike in 2020,when it delivered three.Its still looking over its s

79、houlder at its compatriot Roche,which is runner-up again,but has posted a bigger fall in its pipeline size,putting more road between the two.The remainder of the top five Takeda,Bristol Myers Squibb,and Pfizer each reported that their pipeline world was shrinking slightly too.The biggest climber in

80、terms of places within the top 10 was AstraZeneca,up three places but with only four more drugs,so not really in the conquering Everest scale of ascents.The British company had something of a chequered year,maximizing its feat of being the first to market with a COVID-19 vaccine early in the year,bu

81、t finding its agent falling out of favour as the mRNA vaccines from Pfizer/BioNTech and Moderna overtook it.Only Sanofi and Eli Lilly out of the top 10 also reported growing numbers of R&D projects,with the latter the sole member of the upper echelon for which the trend can be positively reported as

82、 upward.The stagnant or slightly declining pipeline tallies in the top 10 can at least in part be attributed to very low activity amongst the big hitters in the mergers and acquisitions arena.Novartis acquired Cadent Therapeutics early in the year,while Pfizer hitched its wagon to the star of Trilli

83、um Therapeutics,and Lilly chose Protomer Technologies as its fellow traveler.AstraZenecas modest rise can probably be accounted for by its completion of a traveler more sizeable acquisition,Alexion Pharmaceuticals.However,both Sanofi and Merck&Co bucked the trend by buying six and four firms,respect

84、ively:Sanofi thought Kymab,Tidal Therapeutics,Kiadis Pharma,Translate Bio,Kadmon Holdings,and Origimm were just the ticket;while Merck made headway acquiring OncoImmune,Pandion Therapeutics,VelosBio,and,in the years most significant deal,Acceleron Pharma.But against this backdrop,four of the top 10(

85、Roche,Takeda,Bristol Myers Squibb,and Johnson&Johnson)paddled their own canoes and stayed out of the M&A game completely a most unusual state of affairs,but a case of whatever floats your boat.13TABLE 1:Top 25 pharma companies by size of pipelinePOSITION 2022 (2021)COMPANY NO.OF DRUGS IN PIPELINE 20

86、22(2021)NO.OF ORIGINATED DRUGS 2022TREND1(1)Novartis213(232)1292(2)Roche200(227)1203(3)Takeda184(199)684(4)Bristol Myers Squibb168(177)985(6)Pfizer168(170)1016(9)AstraZeneca161(157)897(5)Merck&Co158(176)778(7)Johnson&Johnson157(162)869(10)Sanofi151(141)8710(11)Eli Lilly142(126)7611(12)GlaxoSmithKlin

87、e131(113)6712(8)AbbVie121(160)4413(14)Boehringer Ingelheim108(97)7914(13)Bayer105(108)7615(15)Otsuka Holdings93(95)4616(37)Jiangsu Hengrui Pharmaceuticals89(52)8017(21)Amgen83(77)6418(17)Eisai80(85)4119(22)Astellas Pharma75(76)4320(20)Daiichi Sankyo75(78)4021(16)Gilead Sciences72(95)4522(24)Regenero

88、n68(64)4123(66)Shanghai Fosun Pharmaceutical68(30)4824(26)Biogen66(64)1925(27)Sumitomo Dainippon Pharma66(61)47Overall,though,the landscape for deals through 2021,while not exactly a desert,was somewhat sparsely populated,with 116 mergers and acquisitions reported across the year,down quite a bit fr

89、om the 142 we reported for 2020.It looks like the stay at home advice induced by COVID was being followed at the corporate transaction level to some extent too.One new frontier has opened in our top 25 chart this year however:China.For the first time,we see not one,but two Chinese-headquartered comp

90、anies have left the runway and entered the stratospheric heights of pharma R&D.Jiangsu Hengrui enters the table at number 16,soaring up from 37,with a colossal 71.2%increase it is portfolio size.Meanwhile,Shanghai Fosun Pharmaceutical makes an even steeper ascent,surging 43 places upwards with a pip

91、eline swollen by 127%.A further Chinese Young Turk,BeiGene,sits at the gates to our chart,at number 26.All in all,this represents something of a landmark moment for Chinese pharma R&D.Its often(erroneously)stated that the only manmade structure you can see from space is of Chinese Source:Pharmaproje

92、cts,January 202214construction the famous Great Wall.But its certainly fair to say that,after a number of years of building a presence at a quite extraordinary rate,novel pharma R&D from China is finally on the map.Biogen and Sumitomo Dainippon are the only other newcomers to the top 25 this year,bu

93、t the former of these is just rebounding back in the chart at number 24 and was in the list of leading companies two years ago anyway.Falling out of the rarefied sky of this chart were Evotec(down 11 places to number 29),Servier(down eight to 31),CSL Limited(down three to 28),and Ligand Pharmaceutic

94、als,which fell somewhat more precipitously from 19 to 32,with a pipeline a third smaller.How do we square the circle of seeing such a sizeable growth in the overall pipeline rate when 14 of the biggest 25 pharmaceutical companies are all reporting actual contractions in their pipeline size?At first

95、glance,it might seem akin to more international visitors arriving somewhere even though the jumbo jets landing there are carrying fewer people.FIGURE 4:Share of the pipeline contributed by top 10 companies,top 25 companies,and companies with just one or two drugs,201122 5%OF TOTAL PIPELINEYEAR201120

96、00025TOP 10TOP 25COS WITH 1 OR 2 DRUGSSource:Pharmaprojects,January 202215As Figure 4 shows,the perception that the biggest companies are generating fewer and fewer of the contents of the overall pipeline is indeed correct.The top 10 companies o

97、nly produced 4.63%of the drugs this year,a new record low,down from 5.27%.Similarly,the top 25s percentage fell from 9.36%to 8.51%,less than half the figure it was a decade ago.However,the contribution from the industrys smallest companies also fell slightly this year.The conclusion must be that its

98、 in the mid-sized companies where most of the pipeline growth is occurring.Nonetheless,the biggest companies are fulfilling a role in providing diverse pipelines,at a time when most smaller companies are tending to specialize in just a handful of therapeutic areas.Figure 5 demonstrates this ably.Not

99、e that there is double-counting in this graph,as drugs can be in development for more than one disease area.FIGURE 5:Disease focus areas of the top 10 pharma companies AstraZeneca10%Alimentary/MetabolicAnticancerAnti-infectiveAntiparasiticBlood and ClottingCardiovascualarDermoatologicalGenitourinary

100、(including sex hormones)Hormonal(excluding sex hormones)ImmunologicalMusculoskeletalNeurologicalRespiratorySensory20%30%40%50%60%70%80%90%100%Bristol Myers SquibbEli LillyJohnson&JohnsonMerck&Co.NovartisPfizerRocheSanofiTakeda%OF PIPELINESource:Pharmaprojects,January 202216The top 10 most visited co

101、untries for tourism in 2020 didnt change much on the previous year,despite a radically altered world.However,compared to 2019,tourism dropped by approximately 74%in 2020,with a total of a billion fewer travellers over the course of the year,making 2020 the worst year in recent history.France managed

102、 to retain its long-cherished top spot,followed by Spain and the US.The list is completed by China,Italy,Turkey,Mexico,Thailand,Germany,and the UK.Early 2021 data suggests that the list for that year was looking exactly the same.Our pharma company top 10 didnt change much either,but lets take a look

103、 at the pipelines of those 10 biggest of big pharmas in a bit more detail.Eight out of the top 10 companies have at least one drug in R&D in all 14 of our therapeutic areas,with just Eli Lilly avoiding antiparasitics and Merck&Co declining to develop hormonal drugs.Bristol Myers Squibb has the great

104、est concentration in a single therapeutic area,with 136 of its 168 drugs(81%)being investigated for at least one form of cancer.In fact,cancer represents the largest segment for all of these firms,with the exception of Eli Lilly,which has slightly more alimentary/metabolic drugs in development.Merck

105、&Co has the largest presence in anti-infectives,its 56 candidates giving it one more than its closest rival in that territory,Sanofi.Talking of anti-infectives,how have the big hitters been tackling COVID this past year?Figure 6 shows how their pipelines stacked up across the three indications we us

106、ed to cover the disease:treatment,prophylaxis,and complications support.Pfizer leads the way with 11 agents in total,building considerably on the four it had this time last year.The company has arguably become the world leader here,on the back of its hugely successful collaboration with BioNTech in

107、vaccinology,followed by what looks to be the best direct antiviral we have thus far in Paxlovid(nirmatrelvir).All of the top 10 bar two Merck&Co and Takeda have bigger COVID pipelines than they did this time last year,with Johnson&Johnson coming in second with nine products.Bristol Myers Squibb has

108、the most antivirals,Pfizer the most vaccines/prophylactics,with Novartis leading the way on therapies for complications of SARS-CoV-2 infection(mostly anti-inflammatories).172DRUG COUNT4681012AstraZenecaBristol Myers SquibbEli LillyJohnson&JohnsonMerck&Co.NovartisPfizerRocheSanofiTakedaProphylaxisTr

109、eatment ComplicationsTotalLets also look in the opposite compass direction,from the worlds currently most common disease,to its rarest.Just as many tour operators specialize in organizing travels to obscure,unexplored,remote and secluded destinations in the back of beyond,known to few tourists,pharm

110、a companies are increasingly seeing that there is money to be made developing drugs for little-known and unexplored conditions.Table 2 lists the top 20 companies by assets against rare diseases,and youll see nine of our above top 10 companies featuring in the first 11 in this list.Of these,Novartis

111、has both the most candidates and the highest percentage of rare disease R&D,although,further down the list,the much smaller Shape Therapeutics has the highest percentage of all.In this table,Eli Lilly has the lowest percentage with just 28.2%of its drugs being developed for a rare disease in stark c

112、ontrast to Novartiss huge 64.8%.FIGURE 6:COVID-19 pipelines at the top 10 pharma companies Source:Pharmaprojects,January 202218TABLE 2:Top 20 pharma companies with a rare disease focusCOMPANY NO.OF DRUGS FOR RARE DISEASES%OF PIPELINENovartis13864.8Bristol Myers Squibb10864.3Pfizer9858.3Roche9648.0Sa

113、nofi9663.6Takeda9250.0AstraZeneca7848.4Johnson&Johnson6943.9GlaxoSmithKline6851.9AbbVie5948.8Merck&Co5534.8Amgen5465.1Bayer4946.7Biogen4060.6Eli Lilly4028.2Eisai3847.5Otsuka Holdings3840.9Shape Therapeutics3769.8BeiGene3655.4Astellas Pharma3445.3Source:Pharmaprojects,January 2022NOTE:A rare disease

114、is defined as one with a prevalence of 1 in 2,000 people in the EU,or affecting fewer than 200,000 people in the US(equivalent to around 1 in 1,600 people).Just as world tourism continues to expand,pandemic-permitting,into ever more obscure destinations(snorkelling among the coral reefs in the tiny

115、island nation of Niue,anyone?No,Id never heard of it either!),the world of pharma continues to grow,with more nooks and crannies in undiscovered companies than ever before.There are 5,416 companies involved in pharma R&D as of January 2022,an increase of 317,representing an expansion rate of 6.2%(se

116、e Figure 7 for the explosion in the number of companies across the past two decades).Like the comparable drug figure,these figures are also higher than those seen last year,but to a much lesser degree:the 2021 data added 283 companies at a growth rate of 5.9%.So,2022 didnt post a stellar increase in

117、 the number of R&D firms like the 11.4%expansion we saw in 2020.The number of newly identified companies in the past year came into dock at 1,042,actually very slightly down on the previous years record-breaking 1,055.But this again is a pretty extraordinary statistic.It means that 19.2%,or almost a

118、 fifth,of all companies developing drugs emerged in the past 12 months.And it also means that a net of 725 firms must have exited via the R&D departure lounge.Some of these will have ceased trading,while others may have gone into hibernation mode,and as they have not released new information on thei

119、r drugs for over a year,we will have moved those drugs to inactive for now and the company thus ceases to be represented as active.Of course,1920011,0002,0003,0006,0002002200320042005200620072008200920000022COMPANY COUNT1,1981,3131,5031,5767,3601,6211,6331

120、,9652,0842,2072,3872,7052,7453,2863,6874,0034,1344,3234,8165,0991,7695,416YEAR4,0005,000FIGURE 7:Total number of companies with active pipelines,200122 Source:Pharmaprojects,January 202220this departure lounge has a revolving door,and a small minority of these firms may yet be readmitted to R&D coun

121、try.Once again,the large continents of Big Pharma are augmented by huge archipelagos of tiny islands of emerging companies.This year,there are 759 firms with two drugs and a massive 1,883 with just one candidate,meaning that,taken together,these mini-enclaves account for almost half(48.8%)of all R&D

122、 firms.Despite both of these numbers increasing over the past year,from 733 and 1,849,respectively,the percentage they account for has fallen from 50.6%,which chimes with the fall in the percentage contribution from these companies to the overall pipeline that we witnessed earlier.Since our travel-t

123、hemed report this year naturally has a geographical bent,lets look at the favourite destinations for pharmaceutical research and development.Like our earlier list of top tourist countries,this hasnt changed very much since last year,as Figure 8 shows.The order of popularity remains the same,but bene

124、ath that,there are some subtle shifts.The percentage of companies headquartered in the US has fallen by 2%,while those in the Rest of Europe category fell by 1%.These falls came at the hands of one country China.Its share of pharma companies leaps from 9%to 12%,a very significant expansion for a sin

125、gle year,reflecting the fact that the number of companies based in that country has shot up by an astounding 43.3%,from 522 to 792.There is truly a boom in R&D going on there.FIGURE 8:Distribution of R&D companies by HQ country/region,2021USARest Of EuropeRest Of Asia PacificChinaUKCanadaJapanGerman

126、yFranceC&S America/Africa14%13%9%46%5%4%3%2%3%1%Figure 8:Distribution of R&D companies by HQ country/region,2021 and 2022202121While Figure 8 gives you the nationalities,if you like,of the travellers on the pharma tour bus,Table 3 gives more of a sense of where they are currently visiting.It looks a

127、t all drugs in active R&D and where their development is reported to be taking place.Each drug is counted once for each country it is in development in.Using this metric,the US comes in with 53.4%of all drugs in R&D being in development there,by some distance the biggest proportion for a single coun

128、try.China here is the second biggest individual country,covering 20.8%of all drug R&D worldwide.The table lists all countries with over a thousand drugs in development,and its notable that there is a strong presence from Central and Eastern Europe.USARest Of EuropeRest Of Asia PacificChinaUKCanadaJa

129、panGermanyFranceC&S America/Africa13%13%12%44%5%4%3%2%3%1%FIGURE 8:Distribution of R&D companies by HQ country/region,2022202222TABLE 3:Where is R&D actually occurring?COUNTRY NO.OF DRUGS%OF PIPELINEUS10,73653.4China4,18920.8UK2,88714.4South Korea2,62713.1Germany2,29911.4Canada2,18210.9France2,05710

130、.2Australia2,01010.0Japan1,9319.6Spain1,9099.5Netherlands1,6808.4Belgium1,6088.0Italy1,6038.0Poland1,4777.3Sweden1,4027.0Denmark1,3526.7Switzerland1,3466.7Hungary1,2586.3Czech Republic1,2486.2Austria1,2206.1Taiwan,China1,1205.6Ireland1,0865.4Bulgaria1,0825.4Finland1,0795.4Portugal1,0325.1Romania1,02

131、65.1Greece1,0185.1Norway1,0145.0Israel1,0065.0Source:Pharmaprojects January 202223One of the beauties of twenty-first-century tourism,at least pre-COVID,and almost certainly again post-COVID,is how truly international it is.One can,pretty much,take a holiday anywhere in the world.Whether that might

132、mean relaxing by the pool and enjoying the nightlife in a resort like Puerto Vallarta,skiing in the Alps,or trekking through the rainforests of Borneo,few places are off-limits to the tourist these days.Our company section this year again shows how totally international pharma R&D has become,especia

133、lly now that China has come to the party big-time.And although tourism has taken a major hit from the pandemic,pharma R&D has clearly not in fact the opposite is more the case.More drugs and more companies are offering an international smorgasbord of drugs in development.“Travel makes a wise man bet

134、ter but a fool worse.”Thomas Fuller24Taking in the Varied Scenery:Top TherapiesSpectacular views of the mountains of anticancersOur home planet is quite remarkable.Leaving aside the incredible piece of luck that life evolved here in the first place,it is physically very diverse and beautiful.Take on

135、e of my favourite places,California.Even in this one State,you can choose between the snow-capped mountains of the Sierra Nevada and the grandeur of the Yosemite National Park,the lush,wine-growing Napa Valley,the stunning beaches and coves of the central coast,giant redwoods in the norths National

136、Forests or weird cacti in the souths Joshua Tree National Park,or the arid lifeless bake-off of Death Valley.Incredible diversity,and that is in just one place.The whole world has much more to offer.Diversity is the key to pharma R&D too.Weve already seen how the biggest 10 pharma companies throw th

137、eir nets wide,and in this section,well take a deeper dive through the oceans of pharma R&D and discover how they are teeming with a rich array of different therapeutics,tackling a multitude of multifarious diseases.25candidates.Third-placed anti-infectives posted a more modest 4.7%expansion this yea

138、r,indicating that the COVID-induced 22.4%growth seen last year was something of a one-off,but also that this expanded pipeline has been sustained,rather than falling back.Incredibly,every single therapeutic area grew last year.Cancers rate of growth actually increased across 2021.Figure 10 shows how

139、,from a base-camp of comprising of 26.8%of all drugs in 2010,it has steadily ascended the mountain 20212022NUMBER OF ACTIVE DRUGS1,0002,0003,0004,0005,0006,0007,0008,000THERAPEUTIC AREABiotechnologyAnticancerNeurologicalAnti-InfectiveAlimentary/MetabolicReformulationsMusculoskeletalImmunologicalSens

140、oryRespiratoryDermatologicalCardiovascularBlood&ClottingGenitourinaryHormonalAntiparasiticSource:Pharmaprojects,January 2022FIGURE 9:The R&D pipeline by therapy group,2021 and 2022Figure 9 breaks down drugs by broad therapeutic areas,and again,its worth noting that drugs can be counted in more than

141、one column here if they themselves have diverse disease targets.We will come back to the leading Biotechnology group later(this isnt really a therapeutic area but it is currently included in this taxonomy).Therapeutically,cancer continues to top the league,with 7,772 drugs in its pipeline this year,

142、an inflation-busting increase of 14.0%.Coming in second are neurologicals with a 7.8%rise to 3,301 26to the heights of 39.0%this year,a lofty position from where it can look down at all of the other therapeutic areas far in the valleys below.If the therapeutic areas are the continents of pharma R&D,

143、lets break things down further to the country level,and examine the pipeline by how it splits out across the 241 individual therapeutic categories.The Anticancer,immunological category has the biggest landmass for the fourth year in a row,expanding its territory by a further 15.2%.Both the categorie

144、s at the number two and number three positions also posted big increases,with the general anticancer category(Anticancer,other)up 17.7%,and Gene therapy swelling by a remarkable 23.3%.With jumbo expansions seen across the top three,the next 10 categories 22.0%OF TOTAL PIPELINEYEAR20013201

145、420002124.026.028.030.032.034.036.038.040.0202226.828.029.530.129.329.330.432.634.135.236.737.539.0Source:Pharmaprojects,January 2022FIGURE 10:Proportion of the pipeline which is in development for cancer,20102227post still significant,if slightly less humungous,rises.But unlik

146、e last year,there is not significant movement in placings,particularly within the top 10.Returning to the top 25 this year are the Dermatological and Antiparkinsonian therapeutic categories,while Urological makes its debut at number 24.These are the only new entrants to this years top 25,appearing a

147、t the expense of two cellular therapy categories which drop to just outside the chart(despite actually reporting increases in the sizes of their Source:Pharmaprojects,January 2022TABLE 4:Top 25 therapeutic categoriesPOSITION 2022 (2021)TherapyNo.of active compounds 2022(2021)TREND1(1)Anticancer,immu

148、nological4,275(3,712)2(2)Anticancer,other3,154(2,680)3(3)Gene therapy1,960(1,589)4(4)Monoclonal antibody,other1,277(1,136)5(6)Antiviral,other998(858)6(9)Neurological993(781)7(5)Prophylactic vaccine,anti-infective983(843)8(7)Ophthalmological,other953(781)9(10)Anti-inflammatory726(639)10(11)Cellular t

149、herapy,chimaeric antigen receptor720(612)11(12)Antidiabetic717(569)12(8)Immunosuppressant713(542)13(14)Musculoskeletal656(521)14(13)GI inflammatory/bowel disorders645(482)15(15)Monoclonal antibody,humanized602(555)16(37)Cognition enhancer600(459)17(21)Respiratory596(446)18(17)Cardiovascular595(444)1

150、9(22)Hepatoprotective573(453)20(20)Neuroprotective569(426)21(16)Dermatological504(411)22(24)Antiparkinsonian489(384)23(66)Monoclonal antibody,human488(494)24(26)Urological485(347)25(27)Analgesic,other484(427)pipelines),plus a third covering reformulations.Cell and gene therapies continue to grow in

151、popularity overall.Pharmaprojects Cell&Gene Therapy dashboard provides additional filters for drugs in these fields,thus giving up a new,improved guidebook to better explore these destinations which,like a new resort,are rapidly developing and changing.28Firstly,Figure 11 shows how the rise of the t

152、wo techniques seems to have been as intimately linked as Buda and Pest.Both therapies emerged in the mid-nineties,hit the doldrums a bit in the mid-noughties,but have really gone stratospheric in the past five years or so.Of course,there is something of a symbiotic relationship going on here too,sin

153、ce many therapeutics involve a combination of both techniques,such as CAR-T therapy,which is cell therapy but involves ex vivo genetic manipulation,and thus is classified as both cell and gene therapy.It is the emergence of such approaches which has been driving the explosion in numbers for both cat

154、egories in the past decade.2940020070200042005200620072008200920000022DRUG COUNTYEAR6008001,0001,2001,4001,6001,8002,000Gene CellFIGURE 11:The ongoing rise of gene and cell therapySource:Pharmaprojects,January 202230With a

155、lot of focus on viruses and delivering viral RNA in the past two years,has this shifted the selection of viral vectors used in gene therapy?As Figure 12 shows,the boom town is adeno-associated virus(AAV)vectors;gene therapies using this vector increased from 341 in 2021 to 466 in 2022.This is also t

156、he vector used in several of the COVID-19 vaccines,including AstraZenecas,so many of us(including myself)have received a dose or two of AAV in the past year.For gene therapy,AAV pulled ahead of what was its nearest rival,adenovirus,which was flat.The bigger change since the comparable graph last yea

157、r is the rise in the use of lentiviruses,which are now the second most popular viral vector for gene therapy,used as they are in ex vivo gene therapy to transfect cells.This additional information was added in subsequent to last years report,hence the apparent increase.Meanwhile,retroviruses similar

158、ly demonstrated robust growth,with herpes simplex viruses and poxviruses also coming in with in double-digit counts.Our new indexing feature covering cell therapy projects allows us to take a voyage around the sea of different cell types now being used in this exceptionally hot area.Figure 13 shows

159、the sun is shining brightly down on T cells;being the basis of the popular CAR-T strategy,its not surprising that this cell type is basking in warm waters.Stem cells of various kinds are the other big beasts here,followed by the growth area of natural killer cells.500300350400450500Adeno-

160、associated virusLentivirusAdenovirusRetrovirusHerpes simplex virusPoxvirusRhabdovirusSendai virusSemian virusNUMBER OF GENE THERAPIESFigure 12:Viral vectors used in gene therapyCELL TYPEPreclinicalPhase I Clinical TrialPhase II ClinicalPhase III Clinical TrialPre-registrationRegisteredLaunchedSuspen

161、ded Source:Pharmaprojects,January 2022FIGURE 12:Viral vectors used in gene therapy31Having viewed the R&D Google map from both a continent and country level,lets zoom in further and look at the individual resorts,cities,and national parks of the specific diseases for which drugs are under developmen

162、t.Table 5 lists the top 25.Breast cancer remains the most populous conurbation,but in the context of an overall 8.22%growth in the pipeline,its addition of just two extra drugs feels more like its city limits are shrinking.Coming up strongly in second place is non-small cell lung cancer,which report

163、s a much more significant 11.5%growth.Still seemingly growing rapidly at number three,up from its number five debut position last year,is the category covering antivirals against SARS-CoV-2.The size of its urban sprawl grew by 22.4%,and its worth remembering that two years ago,this disease wasnt eve

164、n a tiny dot on the map yet.Elsewhere in the top 10,there are mostly a number of other forms of cancer which post more modest population growth.The only other exception to the oncological omnipotence is Alzheimers disease at number eight,which could be said to be having a rather interesting moment i

165、n the sun.The controversial approval of Biogens Aduhelm(aducanumab)seems to have given this area something of a boost,despite that drugs subsequent failure thus far to gain much commercial traction.PreclinicalPhase I Clinical TrialPhase II ClinicalPhase III Clinical TrialPre-registrationRegisteredLa

166、unchedSuspended 05006007008009001000T cellsStem cellsNatural killer cellsConnective tissue cellsBlood cellsAntigen-presenting cellsBone marrow cellsTumour-infiltrating lymphocytesProgenitor cellsSkin cellsTumour cellsOther cell typesNUMBER OF CELL THERAPIESCELL TYPESource:Pharmaprojects,J

167、anuary 2022FIGURE 13:Cell types used in cell therapies32Theres more COVID-related coverage further down our table,with sizeable rises for both COVID prophylaxis(which is where most of the vaccines reside),and drugs for COVID complications.Rheumatoid arthritis seems to be 2022s biggest loser.And ther

168、es just one change to the personnel in pharma R&Ds ruling council of diseases,with renal cancer joining the list at the expense of nociceptive pain.This brings cancers population of the table up to 15 out of the top 25 diseases.POSITION 2022 (2021)THERAPYNO.OF ACTIVE COMPOUNDS 2022(2021)TREND1(1)Can

169、cer,breast888(886)2(2)Cancer,lung,non-small cell832(746)3(3)Infection,coronavirus,novel coronavirus677(553)4(4)Cancer,colorectal663(653)5(6)Cancer,pancreatic591(570)6(9)Cancer,ovarian530(518)7(5)Cancer,prostate509(481)8(7)Alzheimers disease496(436)9(10)Cancer,brain485(460)10(11)Cancer,leukaemia,acut

170、e myelogenous462(430)11(12)Diabetes,Type 2445(418)12(8)Cancer,melanoma437(423)13(14)Infection,coronavirus,novel coronavirus prophylaxis436(347)14(13)Cancer,myeloma431(409)15(15)Arthritis,rheumatoid427(435)16(37)Cancer,liver407(382)17(21)Cancer,head and neck377(357)18(17)Parkinsons disease377(340)19(

171、22)Cancer,gastrointestinal,stomach373(358)20(20)Cancer,lymphoma,non-Hodgkins373(344)21(16)Non-alcoholic steatohepatitis360(340)22(24)COVID-19 complications332(266)23(66)Psoriasis328(315)24(26)Cancer,renal254(256)25(27)Asthma252(250)Source:Pharmaprojects,January 2022TABLE 5:Top 25 diseases/indication

172、s33Interestingly,breaking down the top diseases by region or major market paints something of a different picture.In this analysis(Table 6),non-small lung cancer is actually the biggest disease for R&D in all but one region(Africa).Breast cancer is runner-up everywhere,but as NSCLC is absent complet

173、ely from the top eight in Africa,thats enough to get breast cancer over the line overall.Africa as usual has the most distinct disease development pattern.Its the only place apart from the US to have a COVID indication in its top eight,and also featured are some diseases which are notably prevalent

174、there:HIV/AIDS,haemophilia,and tuberculosis.You can also see that Type 2 diabetes is in the top six for many territories type,despite only coming eleventh overall,and that Canada,China,and Oceania have the most highly concentrated focus on cancer.The pattern of drug development across different cont

175、inents is as unique to them as their landscapes.34TABLE 6:Regional variations in R&D,by diseasePOSITION/REGION12345678AFRICADiabetes,Type 2Cancer,breastInfection,HIV/AIDSArthritis,rheumatoidInfection,coronavirus,novel coronavirusInfection,coronavirus,novel coronavirus prophylaxisHaemophilia AInfecti

176、on,tuberculosisASIACancer,lung,non-small cellCancer,breastCancer,gastrointestinal,stomachDiabetes,Type 2Cancer,gastrointestinal,stomachCancer,liverCancer,pancreaticCancer,myelomaCANADACancer,lung,non-small cellCancer,breastCancer,prostateCancer,leukaemia,acute myelogenousCancer,ovarianCancer,renalCa

177、ncer,myelomaCancer,pancreaticCHINACancer,lung,non-small cellCancer,breastCancer,gastrointestinal,stomachCancer,liverCancer,myelomaCancer,pancreaticCancer,leukaemia,acute myelogenousCancer,ovarianEUCancer,lung,non-small cellCancer,breastArthritis,rheumatoidCancer,ovarianCancer,myelomaDiabetes,Type 2C

178、ancer,Gastrointestinal,stomachCancer,renalEUROPE,NON-EUCancer,lung,non-small cellCancer,breastArthritis,rheumatoidDiabetes,Type 2Cancer,ovarianCancer,Gastrointestinal,stomachCancer,myelomaCancer,renalJAPANCancer,lung,non-small cellCancer,breastDiabetes,Type 2Cancer,gastrointestinal,stomachCancer,pan

179、creaticCancer,myelomaCancer,leukaemia,acute myelogenousCancer,liverOCEANIACancer,lung,non-small cellCancer,breastCancer,colorectalCancer,melanomaCancer,ovarianCancer,myelomaCancer,pancreaticCancer,leukaemia,acute myelogenousSOUTH AMERICACancer,lung,non-small cellCancer,breastArthritis,rheumatoidDiab

180、etes,Type 2Cancer,prostateAsthmaCancer,renalCancer,gastrointestinal,stomachUKCancer,lung,non-small cellCancer,breastCancer,colorectalDiabetes,Type 2Cancer,ovarianCancer,renalCancer,gastrointestinal,stomachCancer,myelomaUSACancer,lung,non-small cellCancer,breastInfection,coronavirus,novel coronavirus

181、Cancer,leukaemia,acute myelogenousCancer,pancreaticCancer,ovarianCancer,myelomaCancer,gastrointestinal,stomachSource:Pharmaprojects,January 2022KEYCancerRespiratoryAlimentary/MetabolicInfectious DiseaseMusculoskeletalBlood&Clotting35With SARS-CoV-2 clearly having been one of the main focuses of the

182、worlds pharma companies over the past couple of years,are we still in COVID boomtown,or has R&D now settled down into something more of a steady state?Figure 14 shows how many drugs were added to the Pharmaprojects database in each month of the pandemic to treat the infection,to prevent the infectio

183、n,or to treat the downstream consequences of the infection.We can definitely see that new R&D here was reported at a much lower rate in year two of the pandemic,as the global vaccine rollout proceeded,and there is some evidence of a decline in the second half of the year compared to the first.With m

184、uch better treatments for hospitalized patients,a plethora of vaccines being available,and now oral antiviral therapies coming onstream to treat outpatients,we may see far fewer anti-COVID remedies emerging during 2022.This will especially be the case should the Omicron wave be the pandemics final i

185、ncursion into mass infection.As we noted earlier,while a lot of the worlds media has understandably been focused on what has become(hopefully briefly)the worlds most prevalent disease,very much the US/China of illnesses,the pharmaceutical industry has also been significantly engaged in tackling Figu

186、re 14:COVID-19 response in years one and two of the pandemic0204060800180Jan-20Feb-20Mar-20Apr-20May-20Jun-20Jul-20Aug-20Sep-20Oct-20Nov-20Dec-20Jan-21Feb-21Mar-21Apr-21May-21Jun-21Jul-21Aug-21Sep-21Oct-21Nov-21Dec-21NUMBER OF NEW DRUGSMONTHSource:Pharmaprojects,January 2022FIGURE 14:COVI

187、D-19 response in years one and two of the pandemic36the worlds rarest diseases,which are more akin to the tiny island states of Micronesia or French Polynesia.While this isnt a new thing,the explosion of interest in recent years is amply illustrated by Figure 15,with 677 rare diseases now being the

188、focus of at least one therapeutic development.Theres been a real Mexican wave here over the past few years,crescendoing up from only 389 in 2014.This year,we report that a total of 6,080 drugs,or 30.2%of all therapeutics,are in development for at least one rare disease.This is up from 5,608 last yea

189、r.389440476509546580608648677050060070080020002020212022NUMBER OF RARE DISEASES WITH ACTIVE DRUG R&DYEARFigure 15:Number of rare diseases being targeted by pharma,201422Source:Pharmaprojects,January 2022FIGURE 15:Number of rare diseases being targeted by pharma,20142

190、237Alimentary/Metabolic Products Anticancer Products Anti-infective Products Antiparasitic Products Blood and Clotting Products Cardiovascular Products Dermatological Products Genitourinary Products(including sex hormones)Hormonal Products(excluding sex hormones)Immunological Products Musculoskeleta

191、l Products Neurological Products Respiratory Products Sensory Products 19%12%14%2%5%3%2%2%6%9%16%2%4%FIGURE 16:Rare diseases by therapeutic areaJust as every tourist destination has some delights to be discovered which are more off the beaten track,every therapeutic area has its lesser-known rare di

192、seases.Figure 16 shows the distribution of rare diseases by the therapeutic area they fit into.Its perhaps not surprising that the alimentary/metabolic group has the largest percentage,as its in this area that many of the obscure single gene defect-related metabolic and enzyme disorders reside.Neuro

193、logicals come in second,another area known for some weird and less than wonderful conditions.Its perhaps a bit more surprising to see anti-infectives in third clearly,there are many infectious agents you can catch which are far Source:Pharmaprojects,January 2022more mysterious and arcane than corona

194、virus.Cancer also seems to have its fair share of less common tumour types.38With rare diseases certainly such a key focus for the pharma industry,Pharmaprojects and our sister product Trialtrove have recently introduced enhanced searching capabilities for rare diseases.While Trialtrove doesnt as ye

195、t curate every rare disease,its coverage is nonetheless impressive.Figure 17 demonstrates the growth in rare disease clinical trial starts across the past decade or so.You can see that,although there was a slight dip in 2020,they were back to record levels in 2021.For more information on the fascina

196、ting subject of clinical trials in rare diseases,island hop over to our white paper on this specific subject here.1,236 1,298 1,202 1,261 1,325 1,490 1,540 1,704 1,807 1,845 1,747 1,862 2004006008001,0001,2001,4001,6001,8002,000200001920202021NUMBER OF TRIAL STARTSFi

197、gure 17:Industry-sponsored rare disease trials by start date,201021Source:Pharmaprojects,January 2022FIGURE 17:Industry-sponsored rare disease trials by start date,20102139While on the subject of clinical trials,lets take a look at the panorama of clinical trials currently underway at the start of 2

198、022(Figure 18).We can see that,as found previously,cancers dominance is even more profound in clinical trials country.There are now over 16,000 oncology(open,closed,or temporarily closed)trials underway,up from over 15,400 a year ago.This number dwarfs second-placed CNS with around 6,000,which is be

199、ing caught up by third-placed infectious disease with over 5,600,the latter,of course,driven to some extent by ongoing anti-COVID activity.The total number of all trials involving treatments,vaccines or supportive therapies against this disease reported thus far is still in the overtaking lane on th

200、e motorway,zooming past 6,500,way more than the 4,000 reported this time last year.The number of these which are currently underway now surpasses 2,500(compared with 2,000 last year),but the number of planned trials is up less,from 1,600 to 1,770.Is this an early sign of trial activity in COVID plat

201、eauing,before perhaps beginning to tail off?I suspect this number will have come down a bit by this time in 2023.2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 Oncology CNS Infectious Disease Metabolic/Endocrinology Auoimmune/Inflammation CardiovascularGenitourinaryVaccines(ID)Ophthalmal

202、ogyTHERAPEUTIC AREANUMBER OF CLINICAL TRIALSII/IIIIII/IIIIIIIII/IVIVSource:Trialtrove,January 2022FIGURE 18:Ongoing clinical trials,by therapeutic area402993263943694343483673783882502692982434025030020001920202021NUMBER OF DRUGSYEAR35040045050033839Orphan

203、 Drug Status GrantedExpedited Review Status GrantedEmergency Authorization GrantedBefore we leave the land of therapies and diseases,lets take a look at how many drugs are using souped-up sports cars to get to their holiday destinations more quickly.Figure 19 shows how many drugs were granted orphan

204、 drug status or expedited review designation each year,and you can see that 2021s tally just outpaced 2020s in both cases.This year,weve also added how many drugs received emergency authorizations,since this was a strategy which really came to the fore during the pandemic.There were 39 instances of

205、this alone in the past year.The world of therapeutics is clearly an expanding one.New and rare diseases give the pharma industry new horizons to explore and fresh Source:Pharmaprojects,January 2022FIGURE 19:Number of drugs receiving Orphan Drug status,Expedited Review designation*,and Emergency Auth

206、orization*,201321“Do not follow where the path may lead.Go instead where there is no path and leave a trail.”Ralph Waldo Emersondestinations to exploit.As the distraction of COVID begins to recede,the pharma industry can continue its travels into novel and exciting terrains and vistas.Data for 2013

207、not complete as we only began systematically recording the dates of these events mid-year.Emergency Authorizations only tracked from 2019.41The Road Less Travelled:Mechanisms and Targets Pharma continues to innovate as once-obscure cultures find their place in the sunIf we are styling diseases as th

208、e destinations in the pharma journey,lets switch our attention to how we interpret and understand our new locations.The mechanisms and targets which the industry uses to deliver therapeutics are in this sense the languages and customs which we must understand first if we are going to really get to g

209、rips with our destination and get the most out of our trip.Although historically some drugs have made it to the market without a detailed understanding of how they actually work,increasingly,the strategy is to divine the relevant pathological processes first and design a drug to undertake a particul

210、ar action.The more you understand,the greater your chances of success.After all,you wouldnt go on holiday to a country which speaks a different language without at least taking a phrase book or translation app.One of the few positive outcomes I can draw from the pandemic is that during the first loc

211、kdown,I resumed my attempts to learn Spanish,using a well-known free online learning tool where you do a few minutes a day,every day.Ive kept this up and am still doing it now.Of course,apart from being a beautiful language to learn,Spanish is a very useful one,being one of the most widely spoken gl

212、obally,and some knowledge of it unlocks most of the continent of South America.In that sense,its like one of our broad mechanisms of action,used across a large range of therapeutics.For every one of those,there are many niche pharmacological strategies and targets of use in only very specific circum

213、stances,like languages only spoken a single specific country,such as Georgian,Kyrgyz,or Tuvaluan.Like researching a particular drug target,learning to speak one of those really makes you a specialist.42Source:Pharmaprojects,January 2022POSITION 2022 (2021)MECHANISM OF ACTIONNO.OF DRUGS 2022(2021)%at

214、 PR,R,or LTREND1(1)Immuno-oncology therapy3,307(2,880)2.12(2)Immunostimulant1,494(1,410)8.63(3)T cell stimulant1,062(906)1.04(4)Immune checkpoint inhibitor575(432)4.95(6)Genome editing280(173)06(9)Gene expression inhibitor262(191)1.97(5)Angiogenesis inhibitor198(190)26.38(7)Protein degrader197(-)1.0

215、9(10)CD3 agonist196(100)2.010(11)Radiopharmaceutical183(174)9.311(12)Immunosuppressant173(181)3712(8)PD-L1 antagonist165(125)3.613(14)Natural killer cell stimulant160(113)014(13)Vascular endothelial growth factor(VEGF)receptor antagonist146(142)24.015(15)Immune checkpoint stimulant145(109)016(37)PD-

216、1 antagonist143(113)12.517(21)Microbiome modulator,live microorganisms115(63)018(17)Glucagon-like peptide 1 receptor agonist111(91)7.319(22)Apoptosis stimulant105(114)17.120(20)ErbB-2 antagonist91(95)15.421(16)Surface glycoprotein (SARS-CoV-2)antagonist84(62)8.322(24)DNA inhibitor79(85)31.623(66)Cel

217、l wall synthesis inhibitor74(73)37.824(26)K-Ras inhibitor73(44)42.525(27)Tumour necrosis factor alpha antagonist73(71)1.4TABLE 7:Top 25 mechanisms of action(pharmacologies)ABBREVIATIONSPR:pre-registrationR:registeredL:launched43Our listing of the top 25 mechanisms of action(Table 7)is dominated by t

218、he pharmacological equivalents of English,Spanish,and French.As our mechanism classification is hierarchical,and includes terms to tag certain types of drugs,it is skewed to favour broader terms.This is because,with over half of the pipeline still at the preclinical phase where often full mechanisti

219、c information is as yet unknown or undisclosed,there tend to be a lot of drugs where only a broad mechanism class can be ascribed.As drugs move up through development stages,these general categorizations are often replaced by something more precise.There are also a number of umbrella terms,created t

220、o permit searching across mechanisms in certain broader categories.One of these,the general immuno-oncology mechanism of action,is atop the summit of this table for another year.This category covers all anticancer strategies where the therapy mobilizes the bodys own immune system to identify and att

221、ack its cancer cells,as opposed to drugs which act directly against a tumour,and is applied to all such drugs,even when a more specific mechanism can be ascribed.There has been a further 14.8%growth in drugs categorized this way,an acceleration on last years 10.6%,despite the fact that the percentag

222、e of these drugs which have reached the post-clinical trials stages of development(pre-registration,registered,launched)is unchanged at a meagre 2.1%.Two subclasses of immuno-oncology drug types,T cell stimulant and immune checkpoint inhibitor,are also in the top five,with the latter reporting a sig

223、nificant swelling of its pipeline,by a massive third.Further down,we see the first arrival in the top 10 of a specific IO-related mechanism,in the shape of the CD3 agonist category.Posting a massive 96%expansion in its pipeline,this category is related to the emerging drug type of bispecific T-cell

224、engager antibodies.IO is well represented further down the table too,with PD-L1 antagonist,natural killer cell stimulant,immune checkpoint stimulant,and PD-1 antagonist all not only present but showing expanded pipelines.Even more striking than the high number of IO agents in development with a low

225、percentage in the post-clinical stages is the entry into the top five of the genome editing category,which has precisely zero drugs at these later phases,and really is flying by the seat of its pants.Nevertheless,this class of drugs showed another extremely significant 61.8%uptick in its pipeline,wh

226、ich,so far,has just one drug which has progressed as far as Phase III CRISPR Therapeutics and Vertex Pharmaceuticals sickle cell disease and beta thalassaemia therapy using autologous CRISPR-Cas9 modified CD34+human haematopoietic stem and progenitor cells,CTX001.The much-vaunted CRISPR technique ac

227、counts for a large proportion of drugs assigned this mechanism of action,along with other gene editing techniques such as TALEN,zinc finger nucleases,and meganucleases.Elsewhere in a table which,in terms of big changes of direction,is usually more of a tanker than an agile racing yacht,there are thr

228、ee big new entries of interest.At number 17,and another category with 0%of drugs at the regulatory stages of R&D,is the category for live microorganism microbiome modulators.There are five such agents at Phase III in this case.At number 21,we see antagonism of the SARS-CoV-2 spike protein,probably t

229、he most famous drug target in the world at the moment,entering the top 25 in only its second year of existence.And with a 65.9%increase it its pipeline size at number 24 is the category of K-Ras inhibitor.This simply seems to be an extremely hot area,with 35 of the 73 drugs with this mechanism all j

230、umping onto this particular bandwagon and into our database within the past 12 months.An even starker illustration of how the language of pharma R&D is evolving rapidly can be seen if we switch our attention to the individual 44POSITION 2022 (2021)THERAPYNO.OF DRUGS 2022(2021)TREND1(3)CD3e molecule1

231、99(149)2(6)CD274 molecule PD-L1194(141)3(1)erb-b2 receptor tyrosine kinase 2 Her2177(163)4(4)CD19 molecule174(144)5(2)epidermal growth factor receptor161(151)6(7)programmed cell death 1 PD-1159(122)7(5)vascular endothelial growth factor A158(142)8(10)glucagon like peptide 1 receptor116(98)9(8)opioid

232、 receptor mu 1104(112)10(23)5-hydroxytryptamine receptor 2A103(60)11(9)nuclear receptor subfamily 3 group C member 1 glucocorticoid receptor96(100)12(20)surface glycoprotein,SARS coronavirus 2 SARS-Cov2 spike91(67)13(16)TNF receptor superfamily member 1791(76)14(17)insulin receptor90(72)15(13)tumor

233、necrosis factor90(89)16(11)cannabinoid receptor 187(96)17(30)KRAS proto-oncogene,GTPase87(54)18(15)membrane spanning 4-domains A183(82)19(14)opioid receptor kappa 179(84)20(12)prostaglandin-endoperoxide synthase 275(96)21(33)CD47 molecule70(52)22(19)TNF receptor superfamily member 970(68)23(24)kinas

234、e insert domain receptor67(58)24(32)fms related tyrosine kinase 366(53)25(29)androgen receptor64(54)TABLE 8:Top 25 drug protein targetsNOTE:NCBI names are used,except for additions in italics made by us for clarity.Source:Pharmaprojects,January 2022protein targets which drugs are hitting.After spend

235、ing just two years at the top,last years most popular protein to hit,Her2(erb-b2 receptor kinase 2),has been deposed by the CD3e molecule,with a pipeline which was swollen by a further third.As we already noted,this is a cornerstone of the emerging bispecific antibody technologies.Meanwhile,the targ

236、et which was consistently number one up until and including 2019,the mu1 opioid receptor,is now languishing down at number nine.Its certainly been all change here.Again,immuno-oncology,which,lets not forget,also only itself emerged in the past decade,is increasing its stranglehold on cancer 45drug d

237、evelopment.The CD274 molecule,better known as PD-L1,has shot up to second place with a similarly healthy pipeline expansion,while its compatriot PD-1 also rises.Meanwhile,CD19,the target used in a significant number of CAR-T cell therapies,also cements its place in the top five.It was once notable h

238、ow our table of top targets was far less oncology-oriented than some of our other analyses.This has clearly now changed,with cancer now holding the top seven target spots,with some of these targets only having been validated for drug development in recent years.The old world is being replaced by a r

239、ecently discovered new one.Theres a perhaps surprising boost for 5-hydroxytryptamine receptor 2A,a comparatively traditional target for drugs to treat psychoses,depression,and anxiety,which seems be experiencing an Indian summer,simply just having a very good year for new drug disclosures,with 43 be

240、ing added through 2021.Theres a less surprising spike if you pardon the pun in the drugs targeting surface glycoprotein,SARS coronavirus 2.And there are new entries into the table for the previously noted K-Ras,CD47,and fms related tyrosine kinase 3.CD47 is yet another immuno-oncology target,with th

241、e vast majority of drugs hitting it being monoclonal antibodies.Fms related tyrosine kinase 3 is better known as FLT3 and is one of the most frequently mutated genes responsible for acute myeloid leukaemia.The androgen receptor also makes a return appearance at the bottom of the listing.Leaving our

242、top 25 this year were the dopamine D2 receptor,the estrogen 1 receptor,transient receptor potential cation channel subfamily V member 1(the vanilloid 1 receptor),and prostaglandin-endoperoxide synthase 1 (COX-1;COX-2 also dropped significantly).46Plenty of new terms in our pharma phrasebook to becom

243、e familiar with,then.And it was another good year for neologisms in the world of target identification.Figure 20 indicates that 2021 was another above average year for targets for which drugs in development were reported for the first time.With 131,it was slightly down on the previous year,but came

244、in as the third best of all time(2011 had an anomalously high figure recorded as bacterial targets were added to the Gene database for the first time).Its particularly impressive,given all the restrictions researchers have been working under during the past two years,that levels of innovation appear

245、 to be at a historic 72733900006200720082009200001920202021NUMBER OF NEW TARGETSYEARSource:Pharmaprojects,January 2022FIGURE 20:Number of new drug protein targets identified by Pharmaprojects,by yearhi

246、gh.The total number of targets currently being hit by drugs in active development also rose,standing now at 1,952,almost a hundred higher than last years 1,858.Lots of exciting new territory to explore.“Man cannot discover new oceans unless he has the courage to lose sight of the shore.”Andre Gide47

247、Planes,Trains and Automobiles:Types of Pipeline DrugsTechnologies advance as industry seeks new ways to navigate the disease highway.In 2021,in most places,travel has not been easy.While restrictions on international trips did ease,at least for a time,there was more to negotiate than just ensuring t

248、hat you had your passport and tickets.I was fortunate to be able to escape a non-existent British summer to Spain late in the season,but this now meant filling in a COVID-related form and showing my vaccine passport to enter the country,taking a lateral flow test two days before returning home and r

249、egistering the results with the UK government,and then taking a PCR test two days after my return.All went smoothly,but the additional paperwork and testing certainly added a layer of stress to what should have been a relaxing vacation.If I had tested positive for COVID in Spain I would have been st

250、uck there.And I do know of at least three sets of friends who did fall foul of the increased regulations,ruining their much-needed holidays.Im sure they would not want to repeat those experiences for all the tea in China.Whatever the rights and wrongs of these travel restrictions,which were introduc

251、ed to try to stop the international spread of new COVID variants(arguably shutting the stable door after the horse had bolted),they were only possible in the first place thanks to advances in biological diagnostic technologies.Who knew that we would all become lab technicians in 2021,running our own

252、 home antigen tests?Even a decade ago,mass production of antigen and PCR tests on the scale we have seen would have been almost unthinkable.The pace at which technologies have evolved since the start of the new millennium is staggering.All of which brings us to an examination of the technologies whi

253、ch the pharma industry is using to deliver drugs;perhaps the equivalents to the planes,trains,and automobiles(and latterly,lateral flow tests)which are needed to deliver us to our chosen destinations.As can be seen in Table 9,while its not quite a case of all roads lead to Rome,by far the biggest pr

254、oportion of the many ways to deliver a drug is still by the traditional chemical synthetic route.However,the table lists the origins of each drug,based on Pharmaprojects origin of material classification,which is another hierarchical classification system.Thus,like the mechanism of action classifica

255、tion,the more general categories prosper in cases of early development where information is scant and more specific data is not yet available.In this classification,there is not an Unknown option,so where no information is available,drugs are assigned to Chemical,synthetic by default,thus inflating

256、its figures somewhat.That being said,the vast majority in this class will be genuine synthesized small molecules,so the figures do still have merit.With a 6.2%increase to 9,565 drugs,we can see that there is still considerable activity in this more traditional drug discovery method,although the shar

257、p-eyed amongst you will have noticed that this is less than our earlier overall pipeline growth rate.48POSITION 2022 (2021)THERAPYNO.OF DRUGS 2022(2021)TREND1(1)Chemical,synthetic9,565(9,007)2(2)Biological,protein,antibody2,681(2,484)3(3)Biological,protein,recombinant865(771)4(4)Biological,cellular,

258、autologous776(758)5(6)Biological,nucleic acid,viral vector680(563)6(9)Biological,cellular,heterologous587(448)7(5)Biological,cellular558(459)8(7)Biological,protein541(562)9(10)Biological,virus particles493(458)10(11)Chemical,synthetic,nucleic acid489(437)11(12)Biological,nucleic acid471(296)12(8)Che

259、mical,synthetic,peptide453(475)13(14)Biological,bacterial cells283(251)14(13)Biological,peptide272(259)15(15)Biological,other237(155)16(37)Natural product,plant215(260)17(21)Biological187(224)18(17)Biological,nucleic acid,non-viral vector184(136)19(22)Biological,peptide,recombinant171(141)20(20)Natu

260、ral product,bacterial55(54)21(16)Chemical,semisynthetic53(57)22(24)Natural product,fungal46(39)23(66)Natural product41(39)24(26)Chemical,synthetic,isomeric24(21)25(27)Natural product,animal23(31)TABLE 9:Top 25 origins of pipeline drugsSource:Pharmaprojects,January 202249If developing drugs via chemi

261、cal synthesis is still something of the juggernaut of R&D,monoclonal antibodies are the high-speed trains:sleek,modern,and efficient.Their presence at number two in the table is cemented on the back of a further 7.9%expansion in their numbers.Further down the top 10,we see sizeable upticks for the n

262、ext-generation luxury aircraft liners of the therapeutic world,with the Biological,nucleic acid,viral vector and Biological,cellular,heterologous categories representing the cutting-edge worlds of gene therapy and cell therapy.0%10%20%30%40%50%60%70%80%90%100%7020004

263、2005200620072008200920000022%OF PIPELINEYEARNon-BiotechBiotechFigure 21:Biological versus non-biological drugs as a percentage of the pipeline,19952022Source:Pharmaprojects,January 2022FIGURE 21:Biological versus non-biological drugs as a percentage of the

264、 pipeline,19952022These days travelling to continental Europe from the UK is largely done via aeroplane,as cheaper flights meant that the options to travel by car and ferry or hovercraft soon seemed old-fashioned and slow.How far is the industry similarly moving over wholesale from small molecule to

265、 shiny new biotechnology?Figure 21 shows that the percentage of the pipeline which can be apportioned to a biotech origin is continuing to creep up.Its now at 44.7%,up an additional 1.8%from last year.At this rate,we might reach the tipping point where biotech moves on to becoming the majority soon

266、after the middle of the current decade.50Despite the continued advance of biotechnology-sourced drugs this year,there has been no significant change in the proportions of the pipeline split by route of delivery(one would normally expect that more biotech drugs means more injectables).The injectable

267、route remains the most common drug delivery route,accounting for 60%of the pipeline,followed by oral drugs with 28%.But,as Figure 22 shows,both of these percentages are essentially unchanged from those seen 12 months ago.FIGURE 22:Pipeline by delivery route,2021 and 2022Source:Pharmaprojects,January

268、 20222021Figure 22:Pipeline by delivery route,2021 and 2022 2021InjectableImplantInhaledOpthalmologicalOralOticRectalTopicalTransdermalVaginal61%4%29%3%2%1%0%0%0%51FIGURE 22:Pipeline by delivery route,2021 and 20222022“Surely,of all the wonders of the world,the horizon is the greatest.”Freya StarkSo

269、urce:Pharmaprojects,January 202219%14%3%2%2%9%2%Figure 22:Pipeline by delivery route,2021 and 2022 20210%0%0%60%1%4%28%4%2%1%InjectableImplantInhaledOpthalmologicalOralOticRectalTopicalTransdermalVaginal52Wonders of the Modern World:The end of this years trip,but the journey continues as pharma roun

270、ds the cornerEvery vacation by definition must come to an end,and now were on the home stretch of our analysis,its almost time for us to pack away the sunscreen and beach towels and start planning our transfer back to the airport.While its not been possible to visit every attraction which pharma has

271、 in our trip,weve certainly seen some wonders of the modern scientific world.The seven wonders of the ancient world are the kind of thing which every schoolchild knows.Less well known are the New Seven Wonders of the World,of which,confusingly,there are eight!In the year 2000,a campaign and a poll w

272、ere started by a private foundation to choose the seven wonders from the modern world.However,the poll was considered unscientific and was ultimately frowned on by UNESCO.Nevertheless,it was reportedly one of largest polls ever run,and presented its results in 2007.As the only survivor of the origin

273、al seven wonders,the Great Pyramids at Giza were granted honorary inclusion in addition to the seven poll winners,which were the Great Wall of China,Petra in Jordan,the Colosseum in Rome,Mexicos Chichn Itz,Machu Picchu in Peru,the Taj Mahal in India,and Rios statue of Christ the Redeemer.I feel priv

274、ileged to have visited three of these already,with several others on my must-see list.If the pharma world held a similar poll on modern world wonders,theres no doubt in my mind what would get my vote:the COVID-19 vaccines.I commented last year on the extraordinary achievement of bringing vaccines fr

275、om bench to populace,crossing the Rubicon in the short space of 10 months.In many respects,we have been extremely fortunate.The earlier outbreaks of SARS and MERS had precipitated a huge amount of basic scientific work,which we were now able to capitalize on.Despite appearances,Rome wasnt built in a

276、 day here.And work on the RNA vaccine technologies was also just coming to fruition at the right time.Lets not forget,however,that we should be grateful that the novel coronavirus proved to be vaccinable in the first place not all viruses are.An unfortunate example is HIV,which we seem to be no clos

277、er to producing a vaccine against almost 40 years after it was first discovered.Just imagine if SARS-CoV-2 had proven to be as difficult a nut to crack.It doesnt bear thinking about.And theres nothing to say that the next zoonotic virus to make the leap into humans wont fall into this class,or have

278、a much higher mortality rate.In that nightmare scenario,it could be Goodnight Vienna.In many respects,we might have gotten away lightly this time.53The real achievement of 2021,however,at least in the so-called developed world,has been the vaccine rollout.At the time of writing in late January,my ow

279、n country,the UK,is reporting 90.9%of the eligible population has received a first dose,with 83.9%receiving a second,and 64.3%having had their third,booster dose.This was a huge logistical achievement,facilitated by our wonderful National Health Service.It is this broad vaccine coverage which seems

280、to have allowed us to ride the Omicron wave while not fully closing down our society and economy again(caveated again with the phrase at the time of writing).While the UK is fortunate to have one of the better vaccine coverages in the world,and a relatively small anti-vaxxer cohort,the picture is le

281、ss rosy elsewhere.It has often been said that no-one is safe until everyone is safe.The way the Omicron variant has swept across the world after its first detection in Africa is proof of this mantra.While vaccination programmes remain woefully incomplete in many of the worlds poorer countries,there

282、is always the chance that another,more dangerous variant could yet emerge,which could evade the current vaccines,sliding the world backwards again.It is estimated that,to get over the acute phase of the pandemic,70%of the worlds population must be fully vaccinated.We are nowhere near that yet latest

283、 estimates put this figure at around 52%.However,a glance at the world league table www.bbc.co.uk/news/world-56237778 reveals many countries in Africa and elsewhere languishing at below the 20%mark.The focus of public health officials must now be to get the vaccines to everyone who still needs them,

284、irrespective of geography and wealth.As we start to emerge from the long shadow of the COVID pandemic,the industry is to be again congratulated for not being thrown off its stride;in fact,it rather has a spring in its step.We have already seen how clinical trial activity bounced back and adjusted ve

285、ry quickly,but lets take a moment to reflect on just how well R&D as a whole has not just survived but flourished.All those work from home orders,all those disruptions to supply chains and the industry still managed to grow massively!It has arrived in 2022 with bigger and more robust pipelines,a sho

286、t in the arm from new technologies,and,importantly,with a hugely enhanced reputation with the majority of the public.I say the majority advisedly,as one unfortunate side-effect of the pandemic is that it has thrust pharma onto a new front in the ever-expanding culture wars.Biomedical science has alw

287、ays been part of this,particularly in the highly contentious(in the US at least)womens right to choose issue.But now anti-vaxxers which were,to an extent,always a thing have grown in volume at least and in numbers probably too.The degree of misinformation and vitriol lain at the pharmaceutical indus

288、try has been unprecedented.There was of course a slew of rumours suggesting that the vaccination rollout was a plan by Bill Gates/the government to gather our data/tag us all,and that our DNA was being altered.All utter nonsense of course,but its concerning how these things spread through social med

289、ia,propagated by those with their own agendas,and targeting those in society who are the most vulnerable.While for the majority,the pharmaceutical industry has emerged more strongly supported by the public than ever before in recent history,for a minority,it has become more evil,profit-motivated and

290、 pervasive than ever.Its something that pharma must remember to keep in its rear-view mirror.With global supply chains still recovering from the battering they received from the pandemic,new threats to global stability seem now to be emerging.Fuel prices have soared,raising the spectre of higher inf

291、lation in many countries.In a not-unrelated threat,at the time of writing,the worlds media is convulsed by the potential invasion of Ukraine by Putins Russia,an event which would send further shockwaves through the global economy.While the US has stabler government than it has had to contend with in

292、 the past few years,its society,like that of many other countries,remains deeply divided.And the future direction of the FDA is unclear.54The Aduhelm debacle,whereby Biogens new Alzheimers drug was controversially approved based largely on biomarker rather than efficacy data,has undoubtedly tarnishe

293、d the agencys reputation somewhat.It also set it at loggerheads with payers,many of whom decided not to fund it,and the molecules future currently remains uncertain.With Dr Robert Califf nominated by President Biden to take over as its new Commissioner,the FDA is at something of a crossroads.So,whil

294、e there is light at the end of the tunnel,its not as if the world is emerging untroubled into the sunlit uplands of the post-pandemic landscape.How do industry experts see the road ahead for 2022?Maina Bhaman,partner at Sofinnova Partners,quoted in In Vivo,stated that“the fundamentals remain strong

295、for biopharma:continuing demand for new medicines and outstanding returns.”As we shall see in the forthcoming supplement to this report,New Active Substances Launched During 2021,the industry seems to still be in pole position in its primary goal of delivering novel therapeutics,having had another p

296、henomenally successful year,and we expect this trend to continue.Financially,pharma still looks to be in the drivers seat.Another of our sister products,Biomedtracker,reported 3,148 pharma deals during 2021,including 1,610 financial deals.Also quoted in In Vivo,Bjrn Odlander,founder and managing par

297、tner of HealthCap,said that he expected VC funding momentum to continue in 2022 for both earlier and later rounds of private financing.Has then,the pandemic actually boosted pharma overall?Speaking to Scrip,Pierre Jacquet,vice-chairman of L.E.K.Consultings healthcare practice,reckoned that“a signifi

298、cant chunk of growth from now to 2026 will come from COVID-19,with$200300bn in potential vaccine and therapeutic sales over the next 45 years”,something which he thought might compensate in part for“a market that starting in 2022 is exposed to more than$150bn in loss of exclusivity over the followin

299、g five years.”In the same article,Jonathan Rigby,CEO of Revolo Biotherapeutics,also saw pandemic-related upsides.“With the ongoing COVID-19 pandemic,biopharma will continue to reinvent how it looks from the corporate to clinical perspective,including incorporation of hybrid employment to virtually r

300、un clinical trials that can allow for enhanced patient participation”,he said.“I expect that these reinventions will lead to a more innovative workforce that is better informed by inclusive and robust clinical trial data.”However,a note of caution was sounded by Hing Wong,CEO of HCW Biologics,who po

301、inted out that“COVID-related research and drug studies have and continue to consume considerable resources.This and the near-record amounts of capital created by the biotechnology industry over the past two years have combined to create a research log jam with contract research organizations and con

302、tract manufacturing organizations unable to keep up with demand for their services.With some CMOs reporting a two-year backlog,drug makers are facing long queues to get CTM clinical trial material manufactured,a situation that could significantly delay preclinical and clinical trials this year.”The

303、truth is very much that things are still in flux.As comedian Lily Tomlin once joked,“the road to success is always under construction”.55Nonetheless,at the start of 2022,the pharma industry looks to be firmly in control at the wheel.There may be many forks and bumps in the road ahead,it may even hit

304、 the occasional roadblock,and it may wander occasionally off the beaten track,but as it leaves the COVID pandemic for dust,it appears to be cruising,foot on the pedal,and full steam ahead.It has very much gone the extra mile in the past two years,giving the green light and going from 0 to 60 in a fe

305、w seconds in its attempts to overtake SARS-CoV-2,a race it finally seems to be winning.As a result,life should hopefully be returning to normal this year,which for many of us,means taking long-cherished holidays and long-planned trips again.Time to start thinking about that vacation.Because travel r

306、eally does broaden the mind.“I havent been everywhere,but its on my list.”Susan SontagABOUT THE AUTHORIan LloydSenior Director,Pharmaprojects&Data IntegrationIan Lloyd is the Senior Director of Pharmaprojects and Data Integration,overseeing the content and analyst services for our drug development s

307、olution.He supports clients in their drug pipeline data requirements and inquiries,providing insight into the best search strategies to answer their drug-related business questions and also identifying and analysing trends in pharma R&D.For the past 30 years,he has authored the“Pharma R&D Annual Rev

308、iew”and its new active substances(NAS)launches supplement.This has become a must-have industry report for those seeking to identify the changing fortunes of drug R&D.Ian joined Pharmaprojects in 1987,when it was part of PJB Publications.It was acquired by Informa in 2003.He previously worked in mole

309、cular biology as a research assistant at the University of Bristol.Optimize your portfolio and licensing strategy with end-to-end intelligence for the global drug development pipelinePharmaprojects and Biomedtracker give you all the intelligence and analysis you need with the granular detail you wan

310、t to make better strategic decisions about your pipeline and portfolio.Do you need to know:What are the optimal in-and out-licensing opportunities for my business?1Who are my competitors and what are they doing in the market?2How many assets in the pipeline are likely to be approved and why?3What is

311、 the future market potential for drugs in the pipeline?4Together,Pharmaprojects and Biomedtracker form the leading end-to-end intelligence solution designed to help you understand the global drug development pipeline,competitive landscape and the so-what of your competitors drugs and trial milestones.THE SOLUTIONThe Pharma R&D Annual Review is here!SIGN UP TODAYDont miss our R&D Webinar on April 28th