Those new BCMA CARs have out of this world efficacy: near-100% response rate, PFS of ~3 years in FIFTH LINE myeloma patients!!! Yes, myeloma is a more responsive tumor type even within hem malignancies but these numbers are still so inspiring... (Table from SVB)

Great comprehensive overview on PD(L)1 market from Cowen. Another demonstration of the capital inefficiency that plagues our industry. Beyond the 4 leading agents, billions were invested in undifferentiated drugs instead of pursuing novel targets 🤷‍♂️

12/12 but it is unclear if this can be done with AAVs...

11/12 So to summarize, short term efficacy looks impressive but it’s not better than SOC and just like many other AAV therapies, follow up is still limited with signs of durability issues. Best case scenario for 4D-150 would be to figure out a way to re-treat every 1-2 years

10/12 So far, 4D-150’s response durability was 36 weeks but based on a comment by the investigator one of the four responders already required rescue anti-VEGF treatment after 13-15 months which suggests the effect may not hold for several years.

8/12 2 – Durability - Gene therapies were originally promoted as “once and done” treatments where a single administration has a long lasting effect. Most gene therapies including 4D-150 are based on AAVs which cannot be administered more than once due to immunogenicity.

9/12 People are trying to solve this with immunosuppressive regimens but so far there is no clear clinical proof of concept in humans. If AAVs can be used only once, they need to exert a long lasting effect in order to justify development (3-5 years, depending on the indication).

6/12 But based on one of the slides this dramatic improvement in CST happens BEFORE the patient was treated so it’s hard to attribute the effect to 4D-150. This is not a show stopper because a single injection of 4D-150 that can replace repeat injections of

7/12 Eylea or Lucentis with a similar clinical effect still has a lot of value, it just removes the best case scenario of superiority over SOC and it also suggests that 4D-150 will not beat Eylea in an ongoing randomized P2.

5/12 would be superior to frequent injections (that result in peaks and troughs in the eye). The company claims an improvement in imaging (CST, measures how “wet” the retina is) but this is primarily driven by a single patient (#4) that had a dramatic reduction early in the study

4/12 Achieving this with an intravitreal shot is a big achievement in itself but there are still two caveats. 1-No clinical improvement -Patients do not seem to improve clinically as measured by visual acuity and imaging, in contrast to the hope that constant anti-VEGF expression

3/12 to be a dose dependent effect for responses (no rescue anti-VEGF) and PK (therapeutic protein in the eye). Safety profile looks benign (company used prophylactic eye drops that were gradually tapered).

2/12 These patients had been highly dependent on anti-VEGF injections so the effect is probably treatment-related. This is also supported by the production of meaningful quantities of the relevant protein (anti-VEGF) in the 4 responders. Despite the small sample size, there seems

1/12 Based on $FDMT’s update last month their wAMD gene therapy (4D-150) works but it may not work well enough to disrupt the market. 4D-150’s efficacy looks convincing: At the 36-week cutoff, 4 out of 5 patients at the highest dose did not require rescue anti-VEGF.

Great figures from Jefferies on NASH efficacy across trials (fibrosis improvement and NASH resolution)

@bigpharmaguy Yes, very disappointing 😥 esp in light of the fact all pts had activating PI3K mutations and had not been previously treated with PI3K/mTOR inhibitors

ADC milestones for 2023 from Morgan Stanley. Multiple shots on goal in NSCLC which could be the next big market for ADCs. Good to see diversity in terms of targets (TROP2, CEACAM5, HER3) payloads (Dxd, DM4, MMAE) and patient selection criteria (IHC, EGFR mut).

Biotech IPOs (still weak) and secondaries (still healthy) from Jefferies

TLV's highway right now

3 most intriguing clin data abstracts at #AACR23 so far imo: $RLAY - mutatnt specific PI3K , prelim P1 data $MRUS - EGFRxLGR5 P2 in head and neck $ALLO - CD70 alloCAR in renal cancer

Deep dive from Morgan Stanley on $SGEN's beta6 integrin program. So far P1 data look promising and opportunity is much bigger than most ADCs in development. This one is on top of my ADC watchlist.