Thread by @OxAnalyst

$OLMA San Antonio abstracts released tomorrow AM, so here’s a brief thread on expectations and how to contextualize the data #SABCS21

What does @OlemaOncology OP-1250 need to score in their Ph1 ER+/HER2 in mBC?

$OLMA Cross-trial of Ph1 SERDs have a wide range of ORRs ranging from 0 - 20%, but that alone doesn’t reflect how SOC has changed over time (ie. use of CDK4/6) or safety trade-offs
 
See $ARVN chart showing background use of Palbo and co. moving earlier in the treatment paradigm

On $ARVN: 471 has been cited by sell-side/mgmt as OP-1250 benchmark

Yee wrongly notes a 21% ORR (+no DoR) - should be 7%; ARVN mgmt has told investors that both uPRs had new lesions before confirmation = SD

So a $1B u/f $PFE deal (up to $2.4B) for 7% ORR and clean safety

$OLMA LifeSci has a great SERD comp table – note the ORR/CBR and mPFS spectrum

Other SERDs like $RDUS Elacestrant (topline hit vs. dealer’s choice in 2L mBC post-CDK4/6, also at SABCS, supports future of SERDs in earlier line tx) not included here due to safety concerns

$OLMA SERD class is plagued by cardiac (bradycardia/QTc) and visual tox. Combo w/ CDK4/6 is inevitable so need to be clean (see ZNTL/LLY & ARVN/PFE) to stay in race

If OP-1250 shows clinically significant brady, this will probably be viewed as ‘just another SERD’ (~$7.7/sh)

$OLMA for OP-1250 to compete, they’ll probably need to post an ORR >9% + no significant brady/QT

Much of sellside hopes to see ‘≥ couple responses in evaluable* patients’ (historically ~70%, so ~20/28) or ~10% ORR w/ Cowen’s Werber specifically citing 15% ORR as upside scenario

$OLMA good to keep in mind that at Jefferies London this week, CEO Bohen reminded investors that they will report *all* AEs, not just those deemed treatment-related

wsw.com/webcast/jeff20…

$OLMA if 0%-low ORR in 1st cut, bulls will cite fact that responses usually take 4-6 mos to occur and should wait for higher doses/mature data/deepening responses in Dec 8 poster & call

But Olema allometric suggests starting in therapeutically active range vs. fulvestrant

$OLMA the street's interpreting Bohen as tempering expectations so uncertainty seems to be priced in + this risk-off tape

Yee with ~50-100% upside if OLMA lowest doses can show a couple of PRs / ~15% ORR and good safety

$OLMA didn’t account for an abstract head fake, but interesting to note no DLTs and confirm in-human steady state at all doses > fulvestrant - ‘clinical activity’ will be debated ad nauseam

see you Dec 8

https://twitter.com/MSollender/status/1461699648586850309

$OLMA tough to keep up with all the fantasy/real data drops, but at first glance this official ORR (not the cherry-picked RP2D ORR) is worse than expected

CBR may not be the headline stat, but 29% vs. $ARVN 42% is troubling

globenewswire.com/news-release/2…

$OLMA OP-1250 waterfall and swimmer plots

$OLMA OP-1250 safety shows 3 patients with Gr4 neutropenia

given future combo with CDK4/6 - a drug class that already experiences a high frequency of neutro - this seems discomforting

https://twitter.com/OxAnalyst/status/1461435354364489739?s=20