All posts by Yi Liu

新冠肺炎研发时间线COVID-19 Timeline

Vaccine Index

vaccine and treatment tracker
$SNY $GSK: available 2H21 recombinant protein S + AS03 (squalene-based)
$JNJ: 1st batch for emergency use early 2021, accel PH1/2 to July. Ph3 started 9.24 Ad26.COV2-S (by Janssen), paused 10.12.
$MRNA Ph3 in early summer 2020, Ph1 safety problem in 100ug and 250ug, trial patient vocal on media, 100ug Ph3 in July, slow to publish Ph1 results, afraid of compare? Data published, decent antibody, Dirk denounced its poor CD8 response, safety. $1.525b for 100m dose from USA. 10.23 Completed enrollment, Interim data expected Nov.
$AZN University of Oxford, commoncold virus (Adenovirus) vector preclinical not enough protection in Monkeys, UK.US.德法意荷预定 3 亿只. Already booked 2B doses without any evidence. 6.23重大突破: pig, monkey OK. 3 cases of neuro SAE already.
$NVAX really impressive titer, NVX-CoV237 $388M from CEPI based on preclinical data, still way below after 1:20 reverse split, receives $1.6B from OWS. Decent CD4 CD8 data. Hard to compare to $DVAX CpG., preclinical PPT. Ph1 PPT. Antibody data and CD4 T cell data may be the best so far compared to mRNA stuff, but can easily be overcome by CpG, no CD8+ T cell data shown. 08.15 60m dose order from UK as early as 1Q21. 10.26 Ph3 Delayed 3 weeks. Use 5ug in Ph3.
$VXRT 25x in 6month, penny loser stock, vaccine tablet, selected for NHP study by Operation Warp Speed
$BNTX $PFE $250M from Singapore Temasek淡马锡; 7.1 BNT162b1 preliminary results promising 1.8~2.8x neutralizing antibodies than recovered patients. Ph2b/3 in late July. Filing by YE20, 1B doses by YE21. BNT162b2 enter Ph3 July. Ph1 results, decent CD8.
$INO initially spiked 100%, data released underwhelming, 94% "overall immunological response rates", no antibody data. partial clinical hold on FDA question about delivery device.
$Medicago Canadian Tabacco plant based VLP vaccine testing Ph1 with $GSK $DVAX adjuvant, stopped recruiting 8.25, 10.23 Received $173M funding and 76M dose supply agreement from Canada government. Trial updated with 12m follow up and SARS-CoV-2 infection as secondary endpts. 11.10 Chose $GSK, no alum weak response for $DVAX CpG1018
$ALT intranasal COVID-19 vaccine candidate, AdCOVID
Valneva 100m dose order from UK government, Dynavax adjuvant only, enter trial YE20. Commercial agreement announced Sunday night
$CVAC IPO NASDAQ 2.5X closed. Data due 4Q. Poor data still rise 10%.

CHINA:
3rd $SVA 灭活疫苗 4.17 Ph1 init in China 5.6 Science, Brazil for Ph3, Prelim Ph2 (day 0,14 schedule) data show 90% neutrolizing Ab. $DVAX only, no 2nd adjuvant; but current Ph3 has no adjuvant. 09.09 Ph2 published good safety, poor potentcy (1/50 NVAX), manufacture inconsistency to Ph1
1st CanSino Adeno-S 载体疫苗 Ph2 军科院陈薇 Ph1 init 3.17 5.21 Lancet Ph1, Canada for Ph3, 6.29 approved for military use, shipment on hold due to political tension; Canada deal cancelled.
4th 国药中国生物北京生物 灭活疫苗 中国疾控中心合作 4.27 6.28 北京生物 Ph1/2揭盲 100% in both 0,21 and 0,28
2nd 国药中国生物武汉生物 灭活疫苗 武汉病毒所合作, 6.16 Ph1/II unblinding 97.6% in 0,14 0,21 cohorts, 0,28 100% seroconversion. 6.23 Ph3 initiated BJ, WH, UAE
6th Clover enters Ph1 with alum, $GSK AS03, $DVAX CpG-1018 all 2 doses. Preclinical data: NHP ab not as good as AS03, Th1 better, fever body weight better post challenge. 2.1 Abandon GSK, go with DVAX CpG-1018 for Ph2/3.
7th mRNA vaccine 6.24 approved for trial
8th medigen entered trial early October with only 3 arms, lo/med/hi all with CpG+Alum
9th 安徽智飞 重组新冠疫苗 全球第二只重组新冠疫苗二聚体加传统佐剂, Cell paper, weaker than 国药

Log:
2020.05.18 world leaders down playing vaccine perspective, Oxford and Moderna efficacy in question
2020.06.03 Op. Warp Speed neglected $INO $NVAX $SNY, chose $PFE $MRNA $AZN $MRK $JNJ
2020.07.13 Fauci blamed by WH. $DVAX CpG may have advantage in CD8 T cell response.
2020.07.20 $AZN #Cansino #Oxford these AdenoVector vaccines poor efficacy[endpts], ref2[science Derek Lowe] , ref3 acs.org
2020.07.25 science article on T cell response.
2020.07.24 suddenly I have two companies critical for COVIDVaccine, $DVAX adjuvant for non-mRNA vaccine and $ABUS LNP tech for mRNA vaccine
2020.07.31 US paid $2.1B $21 per dose for the Sanofi/GSK vaccine, $19.95 per dose for Pfizer’s, $16 per Novavax dose and $4 per AstraZeneca dose.
2020.08.08 Inactivated virus vaccines show no T cell response in Guosen report
2020.08.09 Slaoui interview 这个Slaoui采访还是蛮靠谱的. 1. 他不会屈服于任何压力 2. 高危人群先打 3. 小孩要等传统疫苗 4. 明年夏天恢复正常
2020.08.14 JAMA 发表国药武汉的灭活疫苗一期二期数据,和$MRNA $BNTX $AZN差不多 不如$NVAX 比康希诺强, 使用铝佐剂。
2020.08.16 预防流感伴随新冠,康希诺发表二期,新闻基本都忽略DVAX
2020.08.20 BNTX elderly cohort data published, 50-60% reduction, protection may reduce, two dose s obviously required. b1 b2 no big difference. LNP formulation not disclosed. $ABUS tech?
2020.08.26 FDA talks about Vaccine review on 10.22 before election; Abbott $5 flow based antigen test.
2020.08.30 FDA talks about vaccine EUA again.
2020.09.01 NIH experts question CP EUA and Hahn credibility
2020.09.04 people resist test and tracing as "revolutionaries" "rebels" or does not want friends to know he/she gave them covid; moderna slow enrollment to include more diversity
2020.09.06 Vaccines companies to jointly announce that will not submit to FDA before sufficient data. To avoid FDA political pressure and ensure public trust in vaccine
2020.09.08 $AZN Ph3 on hold due to SAE: inflammation of spinal cord, 2nd case possible, likely dead, bad for all AAV vaccines
2020.09.09 俄罗斯疫苗本来样本量就小,还数据造假
2020.09.12 Pfizer/BNTX upsized enrollment to include more diverse population for safety. Still expect efficacy reading by end of October. Grandpa future quote
2020.09.14 recombinant protein vaccine advantage:  their safety features, easy scale-up, economical, and balanced tetravalent immune response. It also obviates the inherent risk of ADE phenomena associated with chimeric live attenuated vaccine. Also take shorter time to reach protection
2020.09.29 $MRNA publish elderly results, similar level to adults
2020.09.29 check current vaccine in trials, very few with adjuvant, I have found most with MF59, AS03, CpG1018, no new deal for a while
2020.10.12 $JNJ
2020.11.03 CEPI invest up to $328M in Clover, include previous $70M; CEPI COVAX 9-vaccine portfolio
2020.11.09 $PFE $BNTX vaccine 90% effective at reducing COVID symptoms. Caveats: Need details on efficacy against severe disease and among elderly; only longer-term studies can determine longer-term efficacy and safety; complex administration program needed; even with vaccine, we need a much stronger public health response. Stocks: $MRNA $BNTX up big, most COVID stocks down big. $ARCT release data on its LNP-mRNA platform -50% on news. Not sure why. Some says not big pharma backing, some says no single dose effect, prime-boost required. Then fall behind competitors.
2020.11.16 $MRNA 94% effective, $BNTX updated to 95%
2020.11.18 Sinovac publish Ph2 results at Lancet, low titer
2020.11.25 $AZN efficacy 70% on high dose, 90% on half-full low dose, have age cap of 55, weird dose response. Also the half-full schedule is a "lucky mistake". Dirk: MRNA vaccine 50% severe solicited AE on 2nd dose. Won't be a "walk in the park". $JNJ vaccine single dose Adeno vaccine starting 2-dose regime, single dose not going well. New player COVAXX Mei Mei Hu multiple peptide vaccine, trial in Taiwan, strong commitment from emerging market.
2020.11.27 $AZN likely to run another Ph3 to meet FDA standard due to dosing mistake; making room for other candidates, $MRNA $NVAX $ABUS $DVAX up 10-20%
2020.11.28 CEPI on vaccine safety and fair distribution
2020.12.03 $PFE reduced shipment from 100M to 50M due to defective raw material. Fauci says UK analysis was not deep enough
2020.12.05 $MRNA 30/30 severe cases in placebo; FDA VRBPAC EUA review 12.17
2020.12.06 CEPI 2nd Gen (Wave 2) criteria:  -single dose -temp stability -manufacturing scalability -improved or differentiated immune response -new antigens. Candidates to be selected by year-end.
2020.12.11 UQ/CSL terminated due to HIV false positive test. Sanofi/GSK setbacks due to error
2020.12.12 $PFE $BNTX EUA approved. Gottlieb claim credit for Pfizer without mentioning BionTech and others.
2020.12.15 $MRNA briefing doc poorer safety than $BNTX. Approved on Friday after 20:0 AdCom. EUA no details on LNP.
2021.1.1 $AZN approved in UK. $ARCT -54% after data release, poor response.
2021.1.12 Brazil Butantan says general efficacy of 50% barely enough for approval. 100% for severe cases? Time to revive CpG-1018 adjuvanted candidate. Valneva in talks with EU
2021.1.15 learned that immunogen very important S.PP favors neutralizing antibody also RBD219 is promising. Medigen uses B4 phage fibritin to stabilize.
2021.1.20 Pfizer/BionTech showing effective against B1.1.7 variant
2021.1.22 药明康德文章回顾疫苗一般不受突变影响,因为抗原表位多,很难全部绕开
2021.1.25 Moderna SA variant 6X less NAb. working on SA specific booster, mask may still be important; MRK (Merck & CO.) discontinue two attenuated virus vaccine (one based on measles (CEPI candidate), one borrowed from its Ebola tech).
2021.1.29 NVAX data: 96% COVID-19 89% UK variant <50% SA variant  Both moderna and biontech are based on S-2P. Mask will be on for quite a while.
2021.1.30 $JNJ data 72% US  57% SA, 85% severe, mediocre data. Less decline, JNJ executives think T cell is helping. T cell epitope paper.
2021.2.1 CEPI $99M loan for $DVAX CpG-1018 adjuvant; Clover abandon previously chosen GSK/AS03 adjuvant for $DVAX CpG-1018 adjuvant for Ph2/3 study. UK exercise option for additional 40Mil doses Valneva/$DVAX vaccine.
2021.2.3 bioRxiv paper showing "Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines" 1) If true, very good news for the world, no need to develop new vaccine, just use adjuvant to boost existing vaccine. 2) Also potential advantage of WT versus S.2P. Interesting development. 3) ZF2001 RBD vaccine (with alum) is weaker than inactivated BBIBP-CorV.
2021.2.3 $VXRT poor data, CD8 T cell, IgA 100%, no serum neutralizing antibody or IgG. -60%
2021.2.3 Philadelphia based Ocugen to bring India Bharat Biotech's vaccine to the US, stock price rise from $0.29 on December 21 to $18.77 as of 2.8.2021 in ~6 weeks. Crazy!
2021.2.5 Sinovac approved conditionally. Brazil Ph3 results 50% all, 83.7% require treatment, 100% severe and death. Turkey 91%.
2021.2.9 Cansino Pakistan trial result one shot 100% severe 74.8% overall global 65.7% severe 91%. better than $JNJ. $AZN/Oxford activity against UK/Kent variant w/ 75% vs 84% for wt. Poor activity against SA variant, SA to abandon $AZN and choose another vaccine. Will different pre-existing immunity in different countries affecting AAV vaccine efficacy? Pfizer vaccine NAb study results against variant. Similar to BBIBP-CorV and ZF2001 study.
2021.2.28 VRBPAC voted 22-0 for $JNJ vaccine
2021.3.17 SA variant vaccine may be a better all-in-one option than original strain. medrxiv
2021.3.18 $AZN vaccine haunted by blood clot cases, experts claim rate not higher than expected. Confirmed related to Vaccine
2021.3.25 Production problem, lack of raw material hits $NVAX, probably other vaccine producers as well.
2021.4.6 Valneva report positive Ph1/2 data, to initiate Ph3 by end of April.
2021.4.9

AAV, AdV, inject large amount of live virus directly into human body, not natural infection dose and route. How many more SAEs and lives will perish until we abandon AAV and switch to LNP? #CovidVaccine $AZN $JNJ #CanSinoBIO $ABUS #GeneTherapy @DavidJuurlink  Yes, the AstraZeneca vaccine-thrombosis association is causal.  The temporal relationship is strong, it’s not seen with mRNA vaccines, and there’s a plausible mechanism analogous to heparin-induced thrombocytopenia (HIT)

2021.4.12 Sinovac release data 50.7% overall protection, 100% hospitalization and death.

Treatment:

2020.06.16 dexamethasone地塞米松 35% reduction in ventilator patients, -20% in oxygen patients. UK research;
2020.06.24 陈薇团队发现N 端中和抗体,可用于抗体鸡尾酒和疫苗设计
2020.07.01 FDA set bar at 50%
2020.06.01 Eli Lily and AbCellera begin Phase 1 study of LY-CoV555, neutralizing antibody
2020.06.07 君实生物 JS016 enters trial , 2ref, 3ref
2020.06.11 Regeneron antibody (2 ab cocktail) enter trial: prevention in uninfected exposed people + patients.
2020.07.07 BARDA OWS first treatment investment $450M to Regeneron. Dirk speculates $ABUS
2020.07.20 Paper showing low IFN early and high IFN late is the related to severe COVID; UK company inhaled IFNb show promising results
2020.08.03 $REGN antibody works in animals
2020.08.23 FDA announced convalescent serum EUA. subgroup of subgroup of subgroup post hoc. Political influence …
2020.09.14 Eli Lilly JAK inhibitorbaricitinib recovered a median of “approximately one day” sooner than those given remdesivir alone; $PFE has a protease inhibitor antiviral PF-07304814 (same link)
2020.09.29 $REGN antibody cocktail some effect, lower viral load, reduce medical intervention, not so impressive, vaccine needed.
2020.10.11 $LLY mAb cocktail LY-CoV016+055 reduced viral load, hospitalization visits 0.9% vs 5.8% placebo.
2020.10.17 Remdesivir no effect by WHO large trial
2020.10.23 Remdesivir received FDA approval despite WHO trial results.
2020.10.26 GSK collaborate with competitor VIR for COVID
2020.10.31 $REGN good for outpatient, continue to enroll for no or low-flow oxygen, halt high-flow oxygen enrolling
2020.11.26 Less than a month after confidently predicting that its Phase III trial can lead straight to a BLA — and not just an EUA — La Jolla, CA-based Equillium said it won’t start the trial after all for its CD6 inhibitor.
2021.1.26 $LLY and $REGN says NAb reduce 70% hospitalization and 100% death
2021.3.13 $VIR nAb VIR-7831 prevent hospitalization and death