Thread by @syinvesting

Here’s a closer look at TIGIT and its potential in #cancer therapy. This target is primed to gain more traction in immuno-oncology this year. (Thread below)

Key players developing anti-TIGIT therapies are $RHHBY $MRK $BMY $RCUS $ALPMY $BGNE $CGEN $SGEN $MREO $IVBXF & @iTeosTx

TIGIT is an inhibitory receptor expressed by activated T-cells, T-regs & NK cells

- Ligand for TIGIT (PVR) is expressed in multiple tumor types
- Activation suppresses T-cell activity
- Upregulated during PD-1 blockade

@Cancer_Cell paper (open access): cell.com/cancer-cell/fu…

A key TIGIT question is the role of FcƔR and antibody-dependent cell-mediated cytotoxicity (ADCC).

$RHHBY & $MRK support FcƔR ADCC benefit due to T-reg depletion & myeloid cell reprogramming. $RCUS states the opposite as this ADCC activity may also deplete T-effector & NK cells.

$RHHBY Roche has recently been very bullish about anti-TIGIT. Its tiragolumab (wildtype IgG1 antibody, ADCC competent) is in a Phase 3 combo trial with Tecentriq in #SCLC.

Key data readouts are:
- #AACR20 (4/26-4/29): Ph 1b multiple tumors
- #ASCO20 (5/29-6/2): Ph 2 1L #NSCLC

$MRK Merck has a similar anti-TIGIT to $RHHBY. MK-7684 (also ADCC competent) is in a Phase 2 combo trial with Keytruda in 1L #NSCLC.

MK-7684 Phase 1 data in advanced solid tumors were presented at #SITC18. No DLTs were observed.

investors.merck.com/news/press-rel…

$RCUS Arcus Biosciences is a #biotech that has ridden the wave of TIGIT interest this month (+97% MTD; now at ~$800M mkt cap).

AB-154 (not ADCC competent) will report anti-TIGIT 1L #NSCLC interim Ph 2 data in late 2020 / early 2021 in combo with anti-PD-1 +/- A2a/A2b inhibitor.

Good @Vantageanalysis article from @JacobPlieth on iTeos' anti-TIGIT mAb (EOS-448) that entered a Phase 1/2 trial: evaluate.com/vantage/articl…

iTeos is backed by MPM Capital, HBM, 6 Dimensions & Curative Ventures.

@iTeosTx PR: iteostherapeutics.com/news/iteos-the…

(Updated TIGIT table below)

@Vantageanalysis @JacobPlieth @iTeosTx $MREO Odds are that Boxer bought this stake as a sympathy play ahead of upcoming $RHHBY TIGIT readouts at #AACR20 & #ASCO20.

Mereo gained OncoMed’s etigilimab through their #ReverseMerger last year. Note that $CELG gave back full rights in Jun '19.

https://twitter.com/MSollender/status/1234951821430407168

@Vantageanalysis @JacobPlieth @iTeosTx $MRK Merck now has four planned combo trials of MK-7684 (anti-TIGIT) + Keytruda.

These trials are in 1L #NSCLC, PD-1-refractory #melanoma (+anti-CTLA-4), 1L melanoma and neoadjuvant melanoma.

Great coverage by @JacobPlieth & @Vantageanalysis (see below)

evaluate.com/vantage/articl…

@Vantageanalysis @JacobPlieth @iTeosTx Upcoming catalysts in the TIGIT and PVRIG (closely related) space

$RHHBY $MRK $BMY $RCUS $CGEN

@Vantageanalysis @JacobPlieth @iTeosTx $RHHBY Ph 1/2 data from Roche's tiragolumab (anti-TIGIT mAb) are expected in 2Q'20. The efficacy threshold in 1L #NSCLC needs to notably exceed Tecentriq's monotherapy 38% ORR.

Updated TIGIT landscape below (Cowen). $MRK $BMY $RCUS $BGNE $MREO $SGEN $CGEN $AGEN $IVBXF & Potenza

@Vantageanalysis @JacobPlieth @iTeosTx The sizable $125M raise by iTeos marks the interest in novel I/O approaches and TIGIT.

Interesting that Boxer co-led this deal and recently took a 9.8% stake in $MREO:

https://twitter.com/syinvesting/status/1234999498541191170

The upcoming Roche tiragolumab data will be telling... $RHHBY

https://twitter.com/syinvesting/status/1245508747319029760

$RHHBY Roche’s Q1 2020 earnings presentation provides an overview of tiragolumab (anti-TIGIT) trials

Deck: roche.com/dam/jcr:f5b0e8…

#AACR20 $CGEN Compugen's COM701 targets PVRIG, which is expressed on immune cells and when engaged by its ligand PVRL2, it signals to suppress immune responses.

PVRIG is a part of the DNAM axis, along with TIGIT.

@CIR_AACR Feb '19 background paper: cancerimmunolres.aacrjournals.org/content/7/2/257

@CIR_AACR Highlights from LR deep dive into TIGIT & PVRIG including upcoming catalysts, the efficacy bar that Roche's tiragolumab data need to beat in #NSCLC and clinical data for the class to date.

$RHHBY $MRK $BMY $ALPMY $RCUS $CGEN $BGNE $SGEN $IVBXF $MREO @iTeosTx

@CIR_AACR @iTeosTx #ASCO20 $RHHBY 1st TIGIT Ph 2 data (n=135) of tiragolumab + Tecentriq combo in 1L PD-L1+ #NSCLC

Primary analysis:
- ORR: 31.3% vs 16.2%
- mPFS: 5.4 mo vs 3.6 mo (HR=0.57)

6 mo follow-up analysis:
- ORR: 37.3% vs 20.6%
- mPFS: 5.6 mo vs 3.9 mo

Abstract: meetinglibrary.asco.org/record/184799/…

@CIR_AACR @iTeosTx #ASCO20 $RHHBY Additional tiragolumab (anti-TIGIT) + Tecentriq data

PD-L1-high (TPS ≥50%):
- n=58
- ORR: 55.2% vs 17.2%
- mPFS: Not reached vs 3.6 mo (HR=0.33)

PD-L1-low (TPS 1-49%):
- n=77
- ORR: 13.2% vs 15.4%
- mPFS: 4.1 mo vs 3.6 mo (HR=0.85)

PR: businesswire.com/news/home/2020…

@CIR_AACR @iTeosTx How do Roche's Phase 2 TIGIT data in 1L #NSCLC PD-L1-high (TPS ≥50%) patients stack up against competitors? #ASCO20

Here's an analysis by Leerink.

$RHHBY $MRK $BMY $RCUS $CGEN $BGNE $SGEN $ALPMY $IVBXF $MREO @iTeosTx

@CIR_AACR @iTeosTx #AACR20 $RHHBY Looks like Roche's Phase 1 TIGIT abstract is embargoed until 6/22/20: abstractsonline.com/pp8/#!/9045/pr…

"Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors"

@CIR_AACR @iTeosTx $IVBXF Innovent has moved its anti-TIGIT mAb (IBI-939) into Phase 1 human trials in China.

The trial will evaluate IBI-939 as both a monotherapy and as a combo with Tyvyt (anti-PD-1 mAb).

$RHHBY $MRK $BMY $RCUS $ALPMY $BGNE $CGEN $SGEN $MREO

https://twitter.com/JacobPlieth/status/1265189709166325760

@CIR_AACR @iTeosTx #ASCO20 Update: $RHHBY Ph 2 data of tira (anti-TIGIT) + Tecentriq combo in 1L PD-L1+ #NSCLC (median follow-up of 10.9 mo)

ITT (n=135):
- ORR: 37% vs 21%
- mPFS: 5.6 mo vs 3.9 mo (HR=0.58)

PD-L1-high (TPS ≥50%):
- n=58
- ORR: 66% vs 24%
- mPFS: Not reached vs 4.1 mo (HR=0.30)

@CIR_AACR @iTeosTx $MREO Mereo announced the completion of a $70M PIPE and plans to advance etigilimab (anti-TIGIT) into a Phase 1b study in 4Q'20.

Investors include OrbiMed, Vivo, Surveyor, Boxer, Pontifax, Samsara, Commodore, Janus & Aspire.

PR: mereobiopharma.com/news-and-event…

https://twitter.com/syinvesting/status/1234999498541191170

@CIR_AACR @iTeosTx $MREO $MPH Looks like Baker Bros now have a 9.4% stake in Mereo (convertible notes + warrants) that was picked up during last week's deal.

Next update for the TIGIT players is the release of Roche's #AACR20 abstract on 6/22/20.

investegate.co.uk/mereo-biopharm…

@CIR_AACR @iTeosTx $MREO Latest deck provides many details on Mereo's TIGIT program (etigilimab): mereobiopharma.com/media/1465/mer…

Mereo has sufficient drug product and plans to run a 60 patient Phase 1b study in combo with a PD-1 in selected tumor types - study to start in 4Q'20.

h/t @BertrandBio

$SGEN Seattle Genetics announced dosing of the first patient in a Phase 1 trial (n=111) evaluating SEA-TGT (anti-TIGIT mAb) for patients with solid tumors and lymphomas: investor.seattlegenetics.com/press-releases…

SEA-TGT is a nonfucosylated human IgG1 antibody.

Design: clinicaltrials.gov/ct2/show/NCT04…

#AACR20 $RHHBY Phase 1 TIGIT Abstract: abstractsonline.com/pp8/#!/9045/pr…

- P1a monotherapy: 0% ORR (0/24)
- P1b Tecentriq combo: 3 responses in PD-L1+ tumors (NSCLC: 1 CR / 1 PR; HNSCC: 1 PR)
- #NSCLC expansion cohort with combo: 50% ORR (7/14) (1 CR / 6 PRs)

Update is at 9:40am ET.

#AACR20 $RHHBY Phase 1 TIGIT Update

- 12/02/19 data cutoff (abstract cutoff was 4/02/19)
- 46% ORR (6/13) in CIT-Naive PD-L1+ #NSCLC expansion cohort (including 2 CRs)
- Well-tolerated and no DLTs across all doses
- Recommended Phase 2 dose is 600mg Q3W + Tecentriq 1200mg Q3W

$RHHBY $MRK Recap of clinical TIGIT data to date from tiragolumab and MK-7684 (Barclays)

$BMY $RCUS $CGEN $SGEN $MREO $IVBXF $ALPMY $BGNE

Here are some good tidbits from the iTeos S-1 on the role of FcγR and ADCC in anti-TIGIT approaches.

$ITOS $RHHBY $MRK $BMY $RCUS $CGEN $SGEN $MREO $IVBXF $ALPMY $BGNE

https://twitter.com/syinvesting/status/1230994242241224704