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
PHARMA HISTORY: Top 10 BY MARKET CAP
2004: Pfizer “King of Lipids - Lipitor”
2005-11: JNJ “TNF Time - Remicade”
2012: Roche “HER Too - Herceptin”
2013-21: JNJ “Bloody Blockbuster - Imbruvica”
2022-23: Lilly “The Obesity Show - Mounjaro”
Source: Joana Sadowska on the HR APP
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
Breaking Down the Pharma Industry: Profit vs. Revenue
Below is how pharma giants stack up in terms of profit vs. revenue?
Total profit: $173.5B
Total revenue: $972.3B
Profit margin: 17.84%
Source: Reza Zahiri on the HR app!
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
$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
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
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)
😱😱😱 Cell and gene therapy investment, once booming, is now in a slump
"Much less money is flowing into the sector as venture investors focus on technologies with less risk and easier paths to market."
This article is sure to touch a nerve! 😀
📬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
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
❓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
AutoImmune Cell Therapy - what is it worth?: all eyes on the $ARTV IPO today. Nothing like a little old fashioned price discovery to keep you entertained on a Friday.
🔘Kyverna Therapeutics: Their early clinical findings in multiple sclerosis (currently Phase 2) have shown
I have an explanation for this. Pharma is under such pressure to deliver revenues today to replace LOEs most of the R&D budget is going toward later stage studies vs. the early stage portfolio.
One extreme position that has been debated has been that pharma should not be
Very striking how “flat” (Ph1 = Ph2 = Ph3) all these pipelines are considering the inevitable attrition rates. Shows just how dependent pharma has become on clinical-stage acquisitions
The stage is set for biotech turnaround....just need the macro to support a line of sight to realized value creation from new investments. MUCHO dry powder waiting to be deployed.
#biotech
👊PHARMA INDUSTRY POWER RANKINGS
👍🏼👍🏼👍🏼EXCELLENT
1️⃣Johnson & Johnson ($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
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
TOP 10 MOST DIFFICULT TO DRUG TARGETS
1️⃣Transcription Factors
2️⃣RNA
3️⃣Allosteric Mechanisms
4️⃣Pre-fusion Forms of Proteins
5️⃣G Protein-Coupled Receptors (GPCRs)
6️⃣Protein-Protein Interactions (PPIs)
7️⃣Enzymes without Defined Active Sites
8️⃣Intrinsically Disordered Proteins
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
👀 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
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🇯🇵)
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
$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
🚀$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
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
FACT OR FICTION?
LNP DELIVERY BEYOND LIVER
Has the biotech world quietly solved one of the biggest limitations of LNPs? Is delivery beyond the liver ready for prime time?
Like if true; comment if false
🌙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