Alex Tanuki

Biologist and ambitious retail trader.
DISCLAIMER: No investment advice. Just my personal opinion. Do your own research! Assume, I could have a position.

[Alex Tanuki @AlphaHubby]

Long $SLS; they issued a press release: The pivotal ph3 trial REGAL reached 72 of 80 events that are required for eliciting the analysis of the primary endpoint. While it takes longer than expected, I interpret this as a positive sign for good efficacy.
https://t.co/7T945KotdY

[Alex Tanuki @AlphaHubby]

$SLS I'm bullish and the phase 3 readout is imminent. I got Call options with 3 diff. expiry dates.
One can expect a press release next week or in January.
Other catalysts: actual presentation of data at a conference and a potential buy out.

[Alex Tanuki @AlphaHubby]

This is best analysis of $RVMD I have seen so far!
Thank you @mbhullar

[Mandeep Bhullar @mbhullar]

🧬 INVESTMENT ANALYSIS: REVOLUTION MEDICINES ( $RVMD)
Deep dive into the most promising pancreatic cancer program in development.

🧵 MEGA THREAD:

1/ EXECUTIVE SUMMARY
Revolution Medicines has transitioned from platform-discovery biotech to late-stage clinical entity.
Lead asset: Daraxonrasib (RMC-6236)
Target: RAS-addicted Pancreatic Ductal Adenocarcinoma (PDAC)
This is one of the largest unmet needs in oncology.

2/ WHY THIS MATTERS
PDAC is devastating: ▪️ ~90-95% driven by KRAS mutations ▪️ Historical 2L survival: 6-9 months ▪️ Standard chemo PFS: 2-3.5 months
RMC-6236 Phase 1 results: ▪️ Median OS: 14.5 months ▪️ Median PFS: 8.5 months ▪️ 6-month OS rate: 89%
This is unprecedented.
3/ THE NUMBERS
▪️ Market Cap: ~$11B ▪️ Cash: $1.93B ▪️ Burn Rate: ~$305M/quarter ▪️ Runway: Funded into 2027
Peak Sales Potential: $7B+ annually (PDAC + NSCLC)
Conservative US-only model: $230-246M by 2035
The bull case is the broad pan-RAS utility.
4/ PROBABILITY OF SUCCESS

We assign 65-70% probability of FDA approval for 2L PDAC.
Why premium over 40-50% historical benchmark?
▪️ Effect size: PFS >100% improvement over historical controls ▪️ Breakthrough Therapy Designation granted ▪️ Commissioner's National Priority Voucher (CNPV)
5/ THE SCIENCE: TRI-COMPLEX REVOLUTION
RMC-6236 is NOT a traditional covalent inhibitor like sotorasib.
It's a "molecular glue" that forms a ternary complex:
Drug + Cyclophilin A (chaperone) + Active RAS protein
This blocks RAS from signaling downstream → shuts down tumor proliferation.

6/ WHY "PAN-RAS" MATTERS
G12C inhibitors (sotorasib) only work on ONE mutation.
RMC-6236 covers: ▪️ G12D (~40% of PDAC) ▪️ G12V (~30% of PDAC) ▪️ G12R ▪️ Q61X ▪️ And more
Addressable: >90% of PDAC patients vs ~8% for G12C inhibitors.
7/ PHASE 1 EFFICACY DATA (2L PDAC)
Cohort: KRAS G12X mutations (n=~127)

▪️ Median PFS: 8.5 months (vs 2-3.5 mo historical) ▪️ Median OS: 14.5 months (vs 6-9 mo historical) ▪️ ORR: 29% (2L), 22% (3L+) ▪️ Disease Control Rate: 91%
For "cold" PDAC, ORR >20% in 2L is exceptional.
8/ SAFETY PROFILE
Generally well-tolerated but not without toxicity:
Common AEs: ▪️ Rash: 87% (any grade) ▪️ GI toxicity (diarrhea, stomatitis, nausea)

Grade ≥3: ▪️ Rash: 8% ▪️ Stomatitis: 3% ▪️ Diarrhea: 2%
Critical: 0% discontinuations due to TRAEs.
Side effects are manageable.
9/ DOSE MODIFICATIONS
▪️ 35% of patients required dose modifications
But here's the key insight:
Zero discontinuations means the toxicity is manageable with: ▪️ Dose interruptions ▪️ Dose reductions ▪️ Supportive care
This is critical for real-world adoption.
10/ COMPETITIVE LANDSCAPE: STANDARD OF CARE

Current options: ▪️ Gemcitabine/Abraxane ▪️ FOLFIRINOX ▪️ NALIRIFOX
Problems: ▪️ Cytotoxic with severe systemic side effects ▪️ Neutropenia, neuropathy ▪️ Modest efficacy
RMC-6236 shows superior PFS/OS with targeted toxicity profile.
11/ COMPETITOR: MRTX1133 (Mirati/BMS)
Mechanism: Non-covalent KRAS G12D inhibitor
Status: Phase 1/2
Limitation: G12D specific ONLY ▪️ Doesn't cover G12V (~30% of PDAC) ▪️ Doesn't cover G12R

Addressable market: ~40% of PDAC vs >90% for RMC-6236
RMC-6236 wins on coverage.
12/ OTHER COMPETITORS
Eli Lilly (LY3962673): Phase 1, G12D inhibitor
Verastem (VS-7375): Phase 1, G12D inhibitor
Assessment: These are trailing assets.
Unless they show vastly superior safety, unlikely to displace RMC-6236 as first-to-market in broad RAS indication.
13/ COMPETITIVE ADVANTAGES
✅ Broadest coverage: Only agent addressing full RAS mutation spectrum in PDAC
✅ First-mover: Phase 3 enrolling while competitors in Phase 1/2
✅ Oral administration: High convenience vs infusions

✅ Unique mechanism: CypA binding creates high barrier to entry
14/ INTELLECTUAL PROPERTY
Patent Estate: ▪️ Core patents (Warp Drive Bio): Expire ~2031 ▪️ RMC-6236 specific: Expire 2038-2044
Additional Protection: ▪️ Orphan Drug Designation: 7 years US market exclusivity post-approval
Freedom to Operate: Tri-complex mechanism creates IP moat against fast-followers.
15/ REGULATORY PATHWAY
Pivotal Trial: RASolute 302 (Phase 3)
Design: ▪️ Randomized, open-label ▪️ Daraxonrasib 300mg QD vs Investigator's Choice chemo ▪️ Population: 2L Metastatic PDAC

Primary Endpoints: PFS and OS
Data readout: 2026
16/ KEY MILESTONES
▪️ Q4 2025: Complete RASolute 302 enrollment ▪️ 1H 2026: Top-line PFS data ▪️ 2H 2026: NDA submission (if positive) ▪️ Q4 2026 / Q1 2027: FDA approval (accelerated via CNPV)
Timeline is aggressive but achievable.
17/ PROBABILITY OF SUCCESS BREAKDOWN
Phase 3 Execution: 85% → Enrolling well, standard endpoints, drug supply secured
Clinical Success: 65% → 8.5mo PFS provides massive buffer vs 2-3mo control
FDA Approval: 90% → BTD + ODD + CNPV = highly motivated FDA
Commercial Success: 75% → High unmet need ensures rapid uptake

18/ THE CNPV ADVANTAGE
Commissioner's National Priority Voucher is a GAME-CHANGER.
Standard review: 10 months Priority review: 6 months CNPV review: 1-2 MONTHS
Impact: ▪️ Adds 4-5 months of peak sales revenue ▪️ Widens gap vs competitors ▪️ Signals FDA views this as "transformative"
19/ CAPITAL STRUCTURE
Cash: $1.93B Debt: $750M facility available (Royalty Pharma) Burn: ~$1.2B annually Runway: Into 2027
The balance sheet is a FORTRESS.
No near-term dilution risk despite heavy investment.

20/ THE ROYALTY PHARMA DEAL (June 2025)
Structure: ▪️ $250M upfront received ▪️ Up to $1.25B additional funding available ▪️ Synthetic royalty: 4.55% on first $2B sales (declining thereafter)
Critical: This is NON-DILUTIVE to equity.
No massive secondary offering needed to fund Phase 3.
21/ TOP SHAREHOLDERS

▪️ Vanguard: 8.1% ▪️ Farallon Capital: 7.6% ▪️ Janus Henderson: 5.9% ▪️ Wellington: 5.1% ▪️ Baker Bros: 4.9%
Strong institutional support from sophisticated biotech investors.
22/ RISK #1: THE "RASH" FACTOR
87% rash incidence + 35% dose modification rate could be problematic outside academic centers.
If Phase 3 discontinuation rates spike → restrictive label

Impact: Reduced peak sales due to lower real-world compliance.
Mitigation: Education for community oncology.
23/ RISK #2: REGULATORY
FDA generally accepts PFS for full approval in 2L PDAC.
But OS is the gold standard.
Risk: PFS positive but OS detrimental (unlikely given Phase 1 data)
Impact: Approval delay or additional data requirements.

Phase 1 OS data (14.5 mo) provides strong buffer.
24/ RISK #3: FINANCIAL
Burning >$1B annually.
If 2026 readout delayed → capital raise needed at potentially depressed valuation.
Impact: 15-20% equity dilution.
Mitigation: $1.93B cash + $750M Royalty Pharma facility provides substantial runway.
25/ RISK #4: EXECUTION
Scaling from clinical to commercial requires different capabilities.

Mitigation: ▪️ CDO Alan Sandler hired ▪️ SVP Alicia Gardner hired
Management is proactively building commercial infrastructure.
26/ DUE DILIGENCE QUESTIONS
CMC: "Can you detail tri-complex synthesis scalability? Specific yield bottlenecks for commercial supply?"
Safety: "What was the Grade 2 rash management protocol? How replicable in community oncology?"
27/ MORE DD QUESTIONS

CNPV: "Does the voucher require rolling CMC submission? Is manufacturing validation on track for accelerated timeline?"
Royalty: "Does the synthetic royalty cap extinguish after a certain return multiple, or perpetual for patent life?"
28/ COMBINATION STRATEGY QUESTION
"What is the biological rationale and preliminary safety data for combination with pembrolizumab (Keytruda) in MSS PDAC?"
Context: MSS tumors typically unresponsive to checkpoint inhibitors. This could expand the opportunity significantly.
29/ MANAGEMENT TEAM
CEO: Mark Goldsmith, MD, PhD ▪️ Formerly Constellation, Third Rock Ventures ▪️ Strong scientific pedigree
Scientific Advisory Board: ▪️ Frank McCormick (RAS expert)
Track Record: Consistently met timeline guidance on Phase 1 initiation, data readouts, Phase 3 initiation.

30/ MANAGEMENT FINANCIAL SOPHISTICATION
The Royalty Pharma deal demonstrates strategic thinking:
▪️ Secured $2B in funding capacity ▪️ Non-dilutive structure ▪️ Locked in at favorable terms before Phase 3 data ▪️ Protected shareholders at critical juncture
This is A+ capital allocation.
31/ VALUATION CONTEXT
Current: ~$11B market cap
Bull Case (1L PDAC + NSCLC approval): $15-18B
Bear Case (Phase 3 failure): >70% correction
The market is pricing in high probability of success.

Risk/reward favors investment given regulatory tailwinds and data quality.
32/ UPSIDE SCENARIO
✅ RASolute 302 hits PFS endpoint (1H 2026) ✅ OS data confirms survival benefit ✅ CNPV enables Q4 2026 / Q1 2027 approval ✅ Rapid commercial uptake in 2L PDAC ✅ Label expansion to 1L PDAC and NSCLC
Target: $15-18B+ market cap
33/ DOWNSIDE SCENARIO
❌ Phase 3 PFS misses statistical significance ❌ Safety signals (rash/GI) lead to high discontinuation ❌ FDA requires additional studies ❌ Delay necessitates dilutive capital raise
Impact: >70% correction given platform concentration.

34/ INVESTMENT THESIS SUMMARY
RVMD represents a HIGH-CONVICTION opportunity in precision oncology.
The convergence of: ▪️ Superior clinical efficacy ▪️ Unique regulatory accelerator (CNPV) ▪️ Fortified balance sheet
Creates compelling risk-reward despite premium valuation.
35/ KEY CATALYSTS TO WATCH
▪️ Q4 2025: RASolute 302 enrollment completion ▪️ 1H 2026: Top-line PFS data (CRITICAL) ▪️ 2H 2026: NDA submission ▪️ Q4 2026/Q1 2027: FDA decision
The next 12-18 months are defining.

36/ FINAL ASSESSMENT
Recommendation: INVEST
Daraxonrasib data is robust. Regulatory pathway is expedited. Balance sheet is secured.
Risks: Safety management, valuation premium.
But the potential to deliver the FIRST pan-RAS inhibitor for PDAC justifies the investment.
37/ KEY METRICS AT A GLANCE
📊 Market Cap: ~$11B 💰 Cash: $1.93B 🔥 Burn: ~$1.2B/year 📈 Peak Sales: $7B+ potential ⏱️ PFS: 8.5 mo (vs 2-3 mo SOC) ⏱️ OS: 14.5 mo (vs 6-9 mo SOC) ✅ ORR: 29% (2L) 🎯 DCR: 91%

38/ THE BOTTOM LINE
Pancreatic cancer has been a "graveyard" for drug development.
RMC-6236 is showing the first real breakthrough in decades.
If Phase 3 confirms Phase 1 data, this becomes a foundational oncology asset.
The risk is real. The opportunity is bigger.

Disclaimer: Not financial advice. Biotech investing involves high risk including total loss of principal. Do your own due diligence.
Sources: https://t.co/4koLYdZia8, https://t.co/7K1d94vM5s, SEC filings, Royalty Pharma, clinical trial databases, peer-reviewed publications

[Alex Tanuki @AlphaHubby]

@RightScopee I do not know the law in the US, but in Germany it is a punishable crime to actively demand the murder of another person! So, yes, the EU laws, this person should be arrested and stand trial in court.

[Psychedelic Alpha @Psyched_Alpha]

Compass Pathways’ Psilocybin Clears First Phase 3 Hurdle

“Rest assured, we’ve got something pretty special here”, $CMPS Chief Commercial Officer Englebert told Psychedelic Alpha.

https://t.co/wF6AOPneSu

[Alex Tanuki @AlphaHubby]

@AntonKreil I work in the health care sector - something you don't know at all.
Free diagnosis: You seem to have Tourette syndrome.
Or extreme narcissism.
Please keep parking in the handicap spots and stick to trading rather than biology/medicine.
Have a wonderful day!

[Alex Tanuki @AlphaHubby]

$CORT. Called it, albeit with a little delay of the readout of the ROSELLA trial.
Press release today on their positive results with a significant overall survival advantage:
https://t.co/KIrBOupGv8

[Alex Tanuki @AlphaHubby]

1/# I'm long Corcept Therapeutics. $CORT is a commercial stage biotech with a positive cash balance and cash flow so far in 2024. In Q4 / 2024, they expect the read outs of two pivotal phase 3 trials. And it appears others are piling in as well.

[Ray Dalio @RayDalio]

How Countries Go Broke: The Big Cycle

As you probably know by now, I'm in a stage of life that has led me to want to pass along previously undisclosed principles that helped me, rather than to keep them to myself. Over my more than 50 years of operating as a global macro investor and through my research, I discovered some timeless and universal cause/effect relationships that helped me successfully navigate what was likely to happen. These principles are not widely understood and have proven to be invaluable, so I think they can help a lot of people.

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If you want a copy of How Countries Go Broke: The Big Cycle, it's now available for pre-order at Amazon (https://t.co/wcLbnLAaaw), Barnes & Noble (https://t.co/GLWF8EHc2R), and other booksellers. It has just gone to the printer and will be on sale June 3. I have also been sharing parts of it online which you can get for free here: https://t.co/bDfTpi9RRt

#howcountriesgobroke #principles

[Alex Tanuki @AlphaHubby]

$CMPS has been on my watch list for a year now. Time to go long for their Ph3 read out in Q2/2025...

[Melissa archer @melissaarcherr]

Good morning, my second stock to buy today is $CMPS

Buy at current price $3.85

COMP360 shows promise in treating refractory depression and PTSD, with significant clinical trial results and potential long-term economic benefits.

[Alex Tanuki @AlphaHubby]

@CrocsAnalyst $CMPS What is the data source for worsening suicide ideation for pts on COMP360?

[Alex Tanuki @AlphaHubby]

Long $CORT. Yesterday's earnings call did not disappoint! Ph3 ROSELLA trial has a high chance of being positive = CATALYST for more upside.
# of events triggered analysis! I expect a press release in 2-8 weeks from CORT

[Alex Tanuki @AlphaHubby]

After $RILY's unexpected jump up >$6, I reentered into a short position. RILY is a donut !!!!!!!!!!

[Marc Cohodes @AlderLaneEggs]

I wonder what Nomura heard on its Bi-Weekly Litigation and Investigation call that made them walk? $RILY.. When is enough enough ⁦@SECGov⁩ @business

[Alex Tanuki @AlphaHubby]

A very worthwhile tweet by @TheShortBear based on overvaluation in certain sectors

[THE SHORT BEAR @TheShortBear]

Cracks forming.
A few events that made my riskometer flash:

• $COIN breaking down its lows anchored VWAP.

• $MSTR breaking down its multimonth trend line support.

• $PLTR big distribution day and failing to hold 9ema.

• $MSFT breaking its 200ema/ma

• $OKLO parabolic and fail

• $HIMS parabolic into its biggest red day ever

• $TOTAL, BTC, ETH, SOL breaking down or near support breakdown

• Yields falling despite higher inflation expectations and CPI prints

• Retail all in long while smart money selling

• Out of favor markets like China catching a bid as an alternative to the expensive US market.

I’m probably forgetting a lot, but this is just what I can remember on the fly. This is what I want to see from the short side and a major red flag as all speculative centers are breaking down.

Not only are these failing but bulls are digging their heels in.

I am bias of course given I am long China, short Crypto and short certain bubble assets like $PLTR.

Before I get pushback on “but if you bought xyz months ago…. I didn’t short then, I’m shorting since this past week.

The decision to remain long is the same as longing at the open today. Just because you longed then doesn’t mean the position is still right. It’s the dynamic risk/reward that matters from here.

[Alex Tanuki @AlphaHubby]

@CheddarFlow The development of pharmaceuticals is one of the most heavily regulated things you could do. Maybe the sector can profit from deregulation?

[Alex Tanuki @AlphaHubby]

The previous German government coalition had the Green Party as toxic element for the national economy - with an author of children's books as minister for economy, subject he had no clue about.

[Alex Tanuki @AlphaHubby]

Germany: the elections clearly show that the conservatives (CDU/CSU) won but they still need a coalition partner. Most likely the labor party (SPD). Most likely this coalition will be more economy friendly than the previous government coalition.

[Alex Tanuki @AlphaHubby]

industrially produced diamonds cost a fraction of natural diamonds and come without any ethical problems. The short $SIG makes perfect sense to me

[Edwin Dorsey @StockJabber]

Short $SIG and the entire diamond industry is my favorite idea for 2025

Sometimes the best ideas are obvious

[Edwin Dorsey @StockJabber]

Starting today, @FOIAsearch lets any investor search all FOIA requests filed with the SEC. This valuable information helps investors detect undisclosed SEC investigations and much more.

Every year, the SEC spends ~$14 million responding to 10,000+ FOIA requests, which gives some savvy hedge funds an edge.

Specifically, when the SEC responds with a B7A exemption, that indicates a likely undisclosed SEC investigation into the subject company.

With @FOIAsearch every investor has this information. Let me know what you think!

[Alex Tanuki @AlphaHubby]

A nice tool and well explained by Edwin from @StockJabber

[Edwin Dorsey @StockJabber]

Starting today, @FOIAsearch lets any investor search all FOIA requests filed with the SEC. This valuable information helps investors detect undisclosed SEC investigations and much more.

Every year, the SEC spends ~$14 million responding to 10,000+ FOIA requests, which gives some savvy hedge funds an edge.

Specifically, when the SEC responds with a B7A exemption, that indicates a likely undisclosed SEC investigation into the subject company.

With @FOIAsearch every investor has this information. Let me know what you think!