Alexander G

@RNAiAnalyst Why can’t he speak now? I was ready to give REPL benefit of doubt, but after many details of communication revealed I’m not sure. REPL framed their communication as complete alignment, while it was procedural emgagemnt.

@AlexandrG1980 Dr Peter Bross came out on LinkedIn (see also reporting on statnews) and said previous review team wanted to approve. Comment on Linkedin was deleted, Prasad fired Bross. Can it be any more obvious?

Wake up #biotech community. Handpicking drug review staff to direct towards a preordained outcome is political interference from the top and has nothing to do with science or medicine. Not even remotely funny.

@RNAiAnalyst $REPL 's communication with FDA looks like "I looked back to see if she looked back to see if I looked back" situation. REPL lived is "desired" world and mistaken procedural engagement for substantive alignment; FDA communicated "real" feedback.

The FDA's argument that it never really approved of the RP-1 study design clearly does not hold water. What changed is that a junior review team following the orders of Prasad and Makary was put in place. But we all know this. $repl

$REPL someth doesn't sum up here. two quotes from REPL from most recent q bus upt and from CRL:

$REPL Any1 knows what happens with options expiring today? what price they would consider for option settlement. cuz stock open around $1 on Monday and that a big difference to a halted price of $4,7

$REPL ‘s management are not saints. FDA was consistent. $QURE ‘s trajectory depends on what’s actually in minutes. I’d guess base case is BLA fining off 4yr data with app’l early 2027

@Vieczny @kainvests @usmagrad click View all job postings

@AlexandrG1980 @kainvests @usmagrad Where? careers-replimune.icims.com/jobs/intro?has…

@Dancingtapas @RNAiAnalyst if $REPL gets 2nd CRL, today's action looks like total shell game.

@RNAiAnalyst @AlexandrG1980 When the president and his associates are insider trading then all bets are off.

$repl longs getting cold feet 2 days ahead of PDUFA. Please let me be right this time ;).

@augurbio Great drug

How do my followers feel about $STOK at this point?

@RNAiAnalyst @Dancingtapas @CNBC $REPL what is even more symptomatic is that $QURE down too. if i had info on REPL CRL, QURE is the next ticker i'd short after REPL

@Dancingtapas @AlexandrG1980 At least Quakary hasn't gone on @cnbc to pre-announce the rejection as he did with $qure. $repl

@RNAiAnalyst @Dancingtapas @CNBC it is not evening yet. maybe we will see his walking-dead selfie video on how $REPL is not eligible for AA due to SA design and heterogeneous pts pop in trial

@RNAiAnalyst well, not pointing fingers, but same happened with ATRA this and previous year exactly 1-2 days befor CRL.

@AlexandrG1980 Are you alleging insider trading?

@jy201506 would you pls elaborate on KOL skepticism re RP1+nivo? also, for some pts RP1 is the only remaining (immunologically active) intervention available. not even mentioning FAR(!!!) more convenient logistics of RP1 vs Amtagvi

Thank you for your thoughtful analysis as always. Totally agree with your point re: current $IOVA pullback likely due in part to upcoming $REPL binary. A big portion of $IOVA share holders prob took profit/put on hedge post recent $5 high into the Iran war and $REPL PDUFA. any positive news from the Iran war front and REPL CRL could trigger violent rebound. Similar to the PD-1 retreatment skepticism from KOL that you mentioned in your article, I heard skepticisms around the efficacy of RP1+ Nivo from KOLs as well for several other additional reasons. Despite of the large number of PIs writing petition letters for the approval of RP1, my gut feeling is that KOLs who are skeptical about RP1's efficacy aren't minority. re: potential competition from $IMTX's Anzu-cel (aka IMA203), it doesn't worry me much. It's basically an autologous cell therapy that's not curative and with small TAM. High 50% ORR, but 0% CRR, with a mDOR of only 12 months in melanoma. Require PRAME screening and HLA matching which adds logistic challenges and shrinks TAM. Unlike Amtagvi which is a platform readily scalable to several other indications, Anzu-cel can't be readily scaled to many other indications due to it's requirement on positive PRAME expression on the tumor. It will likely share the same fate with Adaptimmune's Afami-cel.

$IOVA (L) Iovance Biotherapeutics: Positioned For Multi-Year Growth, Buy The Pullback $REPL seekingalpha.com/article/488878…

@John_Porter10 what is yr bear thesis? 1st crl?

$REPL When this gets its 2ND CRL on Friday Remember who was here BEFORE all these new posters ;)

@BiotechAutist @Dancingtapas FDA had issues with contribution of components. I guess you can’t fix this by simply adding opdualag. You need to either run sepatate arm for nivo or RP1. Yet, fda said they are fine with design. The whole point of confirmatory trial is get drug approved before perfect evidence

25% enrolled does not mean it's too late to change design. Early in a study is exactly when prospective amendments still happen. Also the clinicaltrials.gov record was updated after the crl, on Sept. 17 while the study was still recruiting, and the comparator basket now includes Opdualag. So yes, they made prospective changes to make the future P3 more acceptable. But making IGNYTE 3 more acceptable going forward is different from curing FDA already saying the filed study was not awc.

1/ I'm all in short on $REPL They got rejected because the filed study was not adequate and well-controlled. Their answer was not to produce a new study. Their answer was to run the same one back. CRL is coming🧵

@BiotechAutist @Dancingtapas given what FDA said in CRL (issues with contribution of components) i doubt confirmatory study was "fixable" without major changes in design. and you can't do major change in design of the study which is 25% enrolled

@AlexandrG1980 @Dancingtapas Yes, they prospectively changed the future P3 design to make that study acceptable. That is not the same as curing the separate deficiency on the current filing. Future study design getting cleaned up does not make the already filed study AWC after the fact.

@BiotechAutist @Dancingtapas it just goes to prove that FDA "demands" can be satisfied without running new study. In CRL FDA said that design of conf study is not ok; 2 months later it was ok

@AlexandrG1980 @Dancingtapas IGNYTE-3 is the ongoing study that is still enrolling. So “could potentially support approval” is about a future path. It is not FDA saying the current filing is suddenly fixed.

@BiotechAutist @Dancingtapas Also:

@Dancingtapas @AlexandrG1980 Not really. “Complete response” here just means REPL tried to respond to the CRL, so FDA legally had to review it as a resubmission. The actual question is still whether they fixed FDA already saying the filed study was not adequate and well-controlled.