FDA Development Paths
1️⃣ Standard Designation: Standard designation is the typical pathway for drug development, involving preclinical studies and three phases of clinical trials to assess safety and efficacy thoroughly.
2️⃣ Orphan Designation: Reserved for drugs targeting rare
11 CLINICAL TRIALS THAT WILL SHAPE MEDICINE IN 2024
🧬 Our eyes are on VERVE-101 as it will be the first gene editing POC in common disease.
Will many patients choose with statin refractory hypercholesterolemia choose gene editing? Likely not in our view.
BUT - this study
1/ 🧠💻AI in Biopharma
Case Study: Roche
We will get more into this in the coming weeks in a Sunday newsletter. Sunday's are where we discuss topics related to emerging biopharma strategy.
But follow this thread for some super cool real life use cases from Roche 🧵👇
👀in-vivo CAR-T will be in the clinic 2024
Two companies to file INDs:
👉🏼Interius BioTherapeutics
👉🏼Umoja Biopharma
🐒Interius reported that B-cell counts were reduced by at least 75% in 15 out of 16 animals
ADC History: 7% Success Rate over 40 years
349: have entered human studies
190: in active development
148: discontinued
11: approved by FDA
348-190=158 either approved or discontinued if remove those still progressing as TBD
11/158 = 7% success rate
REMEMBER WHEN PAYING FOR
Landscape of ADCs by Dr. LoRusso. 11 approved ADCs among 349 ADCs that have entered the clinic (148 discontinued). Developing ADCs for solid tumor is challenging given antigens being “tumor-associated” not “specific” and heterogeneity of cancer cells among many reasons.
#ASCO24
Who are the largest
#biotech
investors and how are they doing (via AUM)
1. Baker Bros - 23B
2. Orbi - $18.3B
3. Deerfield - $15.1B
4. RA - $10.8B
5. Perceptive - $9.5B
Source: Torreya
Epoch 33: 1H23
#Biotech
Hedge Fund Performance
✅Macro impact on biotech 2H23?
✅What biotech hedge funds are buying?
✅What biotech hedge funds are selling?
✅Q2 and 3yr biotech HF performance
(Link to subst**ack in bio)
Private Biotech Step-Up Medians
Seed-Series A: 1.25x (24% down rounds)
Series A - Series B: 1.35x (11% down rounds)
Series B - Series C: 1.13x (33% down rounds)
Series C - forward: 0.86x (68% down rounds)
Flat is the new up if you are lucky.....just brutal out there
$IPSC Clears 6mon complete response
If they get to 12mon PFS cell therapy is back!
CNTY-101 is an allogeneic anti-CD19 iPSC-derived NK cell therapy
🧬✂️ 6 Precision Gene Edits
1️⃣Avoid Tcell rejection: KO B2M
2️⃣Avoid Tcell rejection: KO MHCII
3️⃣Avoid NK Rejection: KI HLA-E
📬mRNA/LNP companies we are most excited about:
1. Orna (Anderson)
2. ReCode (Seigwart)
3. Capstan (Weissman)
4. Strand (Weiss, Irvine)
5. Orbital Therapeutics (Chang, Weissman)
6. Sanofi / Tidal Therapeutics (Irvine)
Who did we miss?
👀This one for the $PFE / $SGEN haters that say Pfizer paid too much
$50-60B in 2030 projected WW sales from 3 $SGEN ADCs
14 ADCs in the $PFE pipeline that will add to those numbers
Source: Guggenheim
👀CROs as a proxy for biotech health
$CRL -12%
“One of the drug industry's biggest service providers shared a chilling message for the industry on Wednesday: Expect early pipelines to shrink and research work to decrease as big pharma companies cut costs.”
“The Wilmington,
Momentum Growing in Cell & Gene Therapy
3️⃣4️⃣C> FDA approvals in 2023
5️⃣ in the last 6mon
𝐇𝐚𝐞𝐦𝐚𝐭𝐨𝐥𝐨𝐠𝐲 (20 products):
- 2 for the treatment of multiple myeloma
- 4 for the treatment of lymphoma
- 2 for haemophilia
- 10 for cell transplant-based therapies
- 2 recently
10 BOLD BOWTIEDBIOTECH PROJECTIONS FOR 2024
1) Subdued Enthusiasm for Oral GLP-1: Structure Therapeutics $GPCR winds up with the only acceptable safety profile, but with a moderate 10% weight loss at 40+ weeks. The product finds a significant niche in a patient subsegment
CANCER VACCINES: Tomorrow morning we will have a BIG write-up on a massive binary cancer vaccine readout coming up...5:30am ET!
(l!nk to substa*ck in b!o)
CAR-T therapy for multiple sclerosis enters US trials for first time $KYTX $BMY
🧠 Going for immune rest in the brain
☢️ The neurotox issue will be interesting to monitor - BBB is decorated in CD19 and there are many cells all over the brain with it.
MS $BMY (UW) multiple new products will need to accelerate to build confidence that
the company can replace ~$30bn in LOE revenue between now and 2030. More M&A needed there $XBI
ADC Innovators take note!
Want to get the attention of investors?
Let pharma work on the targeting
Next wave innovation includes:
💡 Recycling optimization to enhance tissue delivery
💡 Maximizing drug-to-antibody loading ratios
💡 Potency enhancement via multi-payload loading
📢Emerging Science I am excited about
1. Targeted Delivery
2. Synthetic Protein Design
3. Beyond Cas9
4. Full length Gene Knock-in
5. In-situ reprogramming
6. In-vivo CART
7. Synthetic DNA
9. Immune Barriers in Oncology
10. CART beyond Oncology
No small mol IYKYK
#biotech
Jefferies: Most likely
#Biotech
M&A 2023
Nice visual on potential non-risk adjusted revenue value of each - the 🔑 factor as pharma is hunting for revenues
$ALNY $ARGX $KRTX $MDGL $NTLA $RDRX $APLS $ITCI $CYTK $ASND $VTYX $AXSM $PCVX $BMRN $FGEN
❓Did you know?
The chance of a drug making it through clinical trials (Ph1 -> Approval) has jumped from 5.8% in 2022 to 10.8% in 2023. While not at historic highs, it's a significant improvement.
More on this coming shortly in Sunday's newsletter which will focus on clinical
CAR T vs TCR Approaches
(1) A chimeric antigen receptor (CAR) is a modular, synthetic receptor that endows T cells with different targeting abilities. Several emerging engineering approaches aim to improve the safety, specificity, and efficacy of CAR therapies.
(2) Engineered
I have an explanation for this. Pharma is under such pressure to deliver revenues today to replace LOEs most of the R&D budget is going toward later stage studies vs. the early stage portfolio.
One extreme position that has been debated has been that pharma should not be
Very striking how “flat” (Ph1 = Ph2 = Ph3) all these pipelines are considering the inevitable attrition rates. Shows just how dependent pharma has become on clinical-stage acquisitions
The stage is set for biotech turnaround....just need the macro to support a line of sight to realized value creation from new investments. MUCHO dry powder waiting to be deployed.
#biotech
👊PHARMA INDUSTRY POWER RANKINGS
👍🏼👍🏼👍🏼EXCELLENT
1️⃣Johnson & Johnson ($JNJ)
Strength: Strong scale advantage and a significant number of blockbuster drugs.
Weakness: No major weaknesses noted; however, it lacks diversification in other concentration areas like therapeutic
1/ 🫁🧬 Seigwart lab out with in-vivo Gene Editing in lung!!!! 🫁🧬
LNP-enabled stem cell editing for durable gene correction in genetic lung diseases like cystic fibrosis!
A lot to like here - editing in non-dividing cells, durable expression, facinating lipid chemistry to
💰💸2023 PHARMA M&A
$ABBV pads neuroscience portfolio with $8.7B deal to acquire $CERE
Capitalizing on share price crash, $AZN inks $1.8B CinCor takeover for blood pressure drug
$CNCE joins SUN PHARMA's symphony for $576M with aim of bringing alopecia treatment to market
$MRK
Interested ADCs? How about CDCs???
Cell–drug conjugates
"By combining living cells with therapeutics, cell–drug conjugates can potentiate the functions of both components, particularly for applications in drug delivery and therapy. The conjugates can be designed to persist in
1/ 🎯FAP TARGETED SOLID TUMOR CAR-T
😎One of the coolest papers I have read recently!
UPenn: Carl June, Steve Albelda, Ellen Pure
😳Solid tumors!
😳Disruption of immune exclusion!
😳CAR-T redosing!
😳CAR-T combos!
Interesting author affil. with
#biotech
⛵️Capatan Tx (in-vivo
👀 Saudi Arabia launches plan to become biotech hub by 2040
…most GPs have made the pilgrimage recently. Follow the money. 💰
https. ://www.fiercebiotech.com/biotech/saudi-arabia-launches-plan-become-biotech-hub-2040
AutoImmune Cell Therapy - what is it worth?: all eyes on the $ARTV IPO today. Nothing like a little old fashioned price discovery to keep you entertained on a Friday.
🔘Kyverna Therapeutics: Their early clinical findings in multiple sclerosis (currently Phase 2) have shown
Moore's Law meets Medicine
RNAi:
Discovery: 1998 (Fire and Mello in C. elegans)
First FDA approval: 2018 (Patisiran for hATTR)
Time to market: 20 years
CRISPR Gene Editing:
Discovery: 2012 (Doudna and Charpentier)
First FDA approval: 2023 (exa-cel for SCD)
Time to market: 11
Interesting answer to the inexorable loss of momentum of🇯🇵pharma R&D
Takeda $TAK,
#Astellas
and
#Sumitomo
Mitsui Banking Announce Master Agreement to Establish Joint Venture Company for Incubation of Early Drug Discovery Programs (R&D originating from🇯🇵)
T Cell Therapy for Autoimmune Disease
See our write-up in the quoted post for our take on this white hot space.
Chart source: Jeff Martin on the HR app
🌙MOONSHOT SCIENCE: in-vivo CAR-T landscape
"27 companies either developing or supplying into the in-vivo engineering of immune cells/CARs space."
Source: Spencer Knight on HR app via Lupagen
🚀$600B+ in pharma deal capacity on sidelines
Its going to be a wild fall when everyone gets back from the Hamptons!
#Biotech
$ROG $MRK $NOVO $NVS $SNY $ABBV $AZN $BMY $REGN $LLY $VRTX $GILD $PFE $GSK $AMGN $BIIB
Source: Jefferies
OBESITY LANDSCAPE $LLY $PFE $NVO
“The obesity opportunity has permeated investor debate over the last 12m, with Novo’s semaglutide and tirzepatide precipitating an area of endocrinology with scope for large growth.”
“Novo retains clear first-mover advantage, LLY's Mounjaro is
$NOVO really has a nice pipeline in Obesity
GLP-1
Oral GLP-1
CagriSema (amylin/calcitonin / GLP-1)
GLP-1/GIP
CBR1
Amycretin
And a TBD triple combo & amylin 2.0 on the way
Large Pharma Has $1 Trillion of M&A Firepower Based on Latest Financials
"A big recent change is that $PFE has dropped off this page following its $SGEN deal."
cc: $VKTX
Source: Stifel
TAM estimates by therapeutic area
Drug Developers will want to book mark
From BMS R&D Day
Oncology 2030
Lung: $61B
MM: $31B
NHL: $27B
Prostate: $20B
Immunology 2030
Pso: $33B
CD: $18B
UC: $10B
Neuro 2030:
MS: $23B
AD: $12B
CV 2030:
Af: $8B
HFpEF: $5B
HCM: $5B
ADC PAYLOAD MATTERS
“Optimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance”
In our view alternative payload strategies have higher PoS vs novel targeting. 🤷♂️
N=79 (64 HER2-pos)
Antibody switching:
The ORR of ADC2 in patients treated with similar payloads was 5.3%. And the ORR of ADC2 in those treated with different payloads was as high as 22.6% (P = .180). (Lots of good info to unpack)
PREDICTION: Biotech IPO market does not recover until 2025-26
🙋♂️WHY? Because at the moment the avg pre money IPO valuations are still sitting >$200-300M level we would guess to be the recent historical mean
🧐PROBLEM: is it is hard to generate sufficient returns to attract
Nice visualization of a key driver of pharma M&A $XBI
Total revenue loss from LOE for 2024-2028 forecasted to be >2x that of the preceding 5-year period
CAR vs TCR
CAR the more mature modality for sure, but TCR therapeutics are going to be interesting to watch play out
Source: Benjamin McLeod on the HR app!