Replimune Group Inc (REPL) Quote

What?

Bk…

ASCO

Initial efficacy and safety of RP1 + nivolumab in patients with anti–PD-1–failed melanoma from the ongoing phase 1/2 IGNYTE study https://meetings.asco.org/abstracts-presentations/219999

Preliminary safety and efficacy results from an open-label, multicenter, phase 1 study of RP2 as a single agent and in combination with nivolumab in a cohort of patients with uveal melanoma https://meetings.asco.org/abstracts-presentations/220091

An open-label clinical trial of RP2 and RP3 oncolytic immunotherapy in combination with atezolizumab and bevacizumab for the treatment of patients with advanced colorectal carcinoma https://meetings.asco.org/abstracts-presentations/225839

An open-label, multicenter study investigating RP3 oncolytic immunotherapy in combination with first- or second-line systemic atezolizumab and bevacizumab therapy in patients with locally advanced unresectable or metastatic hepatocellular carcinoma https://meetings.asco.org/abstracts-presentations/225857

A phase 2, open-label, multicenter study investigating efficacy and safety of RP3 oncolytic immunotherapy combined with other therapies in patients with locoregionally advanced or recurrent squamous cell carcinoma of the head and neck https://meetings.asco.org/abstracts-presentations/225970

It made headlines both sides of the pond. Based on the data (for RP2, as well as RP3), I'm still unsure.

Personally, I would like them to move forward with RP4 (+/- RP5), which has been engineered to secrete a next-gen anti-CTLA-4 [1] (similar to AGEN's), Flt3L (which recruits an important subset of DCs), and angiogenesis inhibitors (targeting the tumour vasculature) [4], in addition to some of the other 'payloads' they have added to RP1/2/3.

Refs:
1 https://jitc.bmj.com/content/10/1/e003488.long
2 https://www.cell.com/immunity/fulltext/S1074-7613(16)30101-7
3 https://www.nature.com/articles/s41591-019-0410-x/
4 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095872

(OT) Identification of a viral 5'leader that augments therapeutic transgene payload production during cancer cell and tumour infection https://jitc.bmj.com/content/11/3/e006408

More here https://www.evaluate.com/vantage/articles/news/trial-results/replimunes-melanoma-success-looks-more-skin-deep

Link to webcast https://www.wsw.com/webcast/cc/repl3/register.aspx?conf=cc&page=repl3&url=https://www.wsw.com/webcast/cc/repl3/1433700

An Investor Day set for the 7th at 8:00 AM ET. It will provide preliminary data from the six-month follow-up of the first 75 patients enrolled in the IGNYTE clinical trial cohort of RP1 combined with Opdivo in anti-PD1 failed melanoma. Additionally, there will be an update on the RP2 and RP3 program as well.

huge: https://nypost.com/2022/09/30/cancerous-tumor-vanishes-with-injection-of-modified-herpes-virus/

PR https://www.biospace.com/article/releases/replimune-provides-new-clinical-data-broad-program-update-and-future-development-strategy-for-its-tumor-directed-oncolytic-immunotherapies/

Slides https://ir.replimune.com/static-files/a620f9c6-dadd-45cc-8406-ee0cf1c9cf3e

Link to webcast https://wsw.com/webcast/cc/repl2/1432638

Members of its executive team and KOLs will host an investor event to present, updated data on Wed March 30, with it beginning at 8:00 a.m. Eastern Time.

The password is: GETICA_220126 https://vimeo.com/674771361

The company will host an investor event in March. The event will review updated data from completed IGNYTE cohorts in non-melanoma skin cancers and melanoma. In addition, they intend to present initial data from the ongoing study in anti-PD1 failed non-melanoma skin cancers and from its ARTACUS trial. Also, will provide a detailed overview of its RP2/3 program, including the PhII trial (around mid-year) development plan. For RP2, an update later this year. With RP3, enrolment in combination with Opdivo should start this quarter, with initial expansion patient data later this year as well.

SITC posters https://ir.replimune.com/static-files/fb937395-5281-41c1-8dba-aca83e1c2c9a https://ir.replimune.com/static-files/c2169e7d-12d4-498e-8ace-a347bb2578b6 https://ir.replimune.com/static-files/be46a132-bfdc-4018-a62f-f37f63864690 https://ir.replimune.com/static-files/b1f8c808-4d22-415a-b0a0-e25191bf8e7c

nice analysis.

Thanks.

Yeah most are Trial in progress updates.

I'm hoping to see some more responses and good DOR from the RP2 trial.

I think the next big data drop comes in early 2022. Its been a quiet year for REPL outside of the Investor Day event

Yes, in Q1 2022

• Initial single agent data in all comers in the RP3 PhI.
• Initial data from RP1 plus Opdivo in anti-PD-1 failed CSCC.
• RP1 single agent initial data in CSCC organ transplant patients.
• Also, details on RP2/3 development strategy.

Then, Q4

• CERPASS (CSCC registration-directed trial) primary read out trigger.
• IGNYTE (anti-PD-1 failed melanoma registration-directed trial) read out.
• RP1 plus Opdivo in anti-PD1 failed NSCLC data.
• RP1 plus Opdivo in anti-PD1 failed CSCC updated.
• RP1 single agent data in CSCC organ transplant patients.
• RP2 liver mets cohort expansion data.
• Initial data from anti-PD-1 combination cohort with RP3.

nice analysis. Yeah most are Trial in progress updates. I think the next big data drop comes in early 2022. Its been a quiet year for REPL outside of the Investor Day event

Looking forward to seeing these updates from SITC.

A number (three) will be TIP posters, so the only clinical update is going to be from the ongoing RP2 (+/- Opdivo) trial. It will be interesting to compare that to ONCR's ONCR-177 (initial clinical data also being presented at the same event), which uses a kitchen sink approach (the transgenes are Flt3L, IL-12, CCL4, anti-CTLA-4 and anti-PD-1, there are differences between the base viruses, but both use HSV-1).

Did MGMT slip up last year and release the abstract content with initial PR of SITC abstract titles? The PR on oct14 2020 included the abstract content and SITC embargo for abstract content unlocks right before the actual conference

No, it was the organisers, with data leaking via their site.

This year I think the abstract embargo lifts Nov 9 2021.

Yes, at 8 am EST.

Looking forward to seeing these updates from SITC. Did MGMT slip up last year and release the abstract content with initial PR of SITC abstract titles? The PR on oct14 2020 included the abstract content and SITC embargo for abstract content unlocks right before the actual conference This year I think the abstract embargo lifts Nov 9 2021.

SITC:

Abstract Title: A phase 1 clinical trial of RP2, an enhanced potency oncolytic HSV expressing an anti-CTLA-4 antibody, as a single agent and combined with nivolumab in patients with advanced solid tumors
Abstract Number: 507
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: ARTACUS: An open-label, multicenter, phase 1b/2 study of RP1 in solid organ transplant recipients with advanced cutaneous malignancies (Trial in Progress presentation)
Abstract Number: 550
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: CERPASS: A randomized, controlled, open-label, phase 2 study of cemiplimab ± RP1 in patients with advanced cutaneous squamous cell carcinoma (Trial in Progress presentation)
Abstract Number: 547
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Abstract Title: IGNYTE: An open-label, multicenter, phase 1/2 (Ph 1/2) clinical trial of RP1 ± nivolumab in patients with advanced solid tumors (Trial in Progress presentation)
Abstract Number: 506
Session Date and Time: November 12-14, 2021 from 7:00 AM ET- 5:00 PM ET
Location: Hall E

Link https://wsw.com/webcast/blair59/panel4/2160224

Dr. Coffin, will participate in a panel titled ''Novel Mechanisms and Strategies for Addressing PD-(L)1 Refractory/Resistant Tumours'' at the William Blair Biotech Focus Conference taking place virtually on Wednesday, July 14, at 4:20 PM ET.

A simultaneous webcast will be available in the Investors section. A replay will be available for approximately three months following the conference.

The PR https://www.globenewswire.com/news-release/2021/06/03/2241138/0/en/Replimune-Provides-Data-Update-from-its-RP1-vusolimogene-oderparepvec-and-RP2-Programs-and-Announces-Plans-to-Expand-the-Development-of-RP2-3-Beyond-Phase-1.html

Slides https://ir.replimune.com/static-files/f4fe3349-e082-4d41-94a1-106ce7e78a23

Link to the webcast https://wsw.com/webcast/cc/repl/1379538

The company will host an investor event to present updated data from its PhII skin cancer cohorts combining RP1 with Opdivo and data from its PhI trial of RP2 alone and in combination with Opdivo. The event will include presentations by Philip Astley-Sparke, Chief Executive Officer, Robert Coffin, Ph.D., President and Chief Research & Development Officer, and Mark Middleton, Professor of Experimental Cancer Medicine in the Department of Oncology, consultant Medical Oncologist at the Oxford Cancer and Haematology Centre and Head of the Department of Oncology at the University of Oxford.

The event will begin at 8:00 a.m. Eastern Time on Thursday, June 3. The webcast and slides will be accessible live under “Events & Presentations” on the Investors page of the company's website.

The posters https://ir.replimune.com/static-files/8ceb7c8e-cf10-4f65-b6ff-30f2aaa3a2d3 https://ir.replimune.com/static-files/7fd01869-644e-4fdd-898e-dfb58a721cfb

Dr. Coffin has said that additional data from RP1 (CSCC and NMSCs) will also be presented at ASCO.

Thanks J
I expect to see something significant very soon

Why the steep drop today?

I haven't been able to find out why.

I hope they plan on releasing something very quick

They will be presenting some data at AACR, but ASCO will be the main event, due to additional data from the RP2 (+/- Opdivo) trial. Last year the data on just nine patients at SITC sent the stock up by around $20-30 (from memory).

AACR https://www.abstractsonline.com/pp8/#!/9325/presentation/4664 https://www.abstractsonline.com/pp8/#!/9325/presentation/2952

Why the steep drop today? If this continues, the supports will fail, and free fall.
I hope they plan on releasing something very quick

Yes, this year;

RP1 + Opdivo, anti-PD1 failed NSCLC initial data
RP1 + Opdivo, anti-PD1 failed CSCC initial data
RP1 single agent initial data in CSCC transplant patients
RP2 + Opdivo initial data in all comers study
RP3 Phase 1 initial single agent data in all comers

Additional updates from all ongoing studies from which initial data has previously been released.

Next year;

CERPASS (CSCC registration directed trial) primary readout
IGNYTE (anti-PD1 failed melanoma registration directed trial) primary readout
RP3 + Opdivo data in all comers study
Potential for initial readouts from other follow on studies with RP2/3.

So is there anything of interest coming in for REPL?

JP Morgan webcast https://jpmorgan.metameetings.net/events/healthcare21/sessions/35490-replimune/webcast

SITC posters:

RP1 https://ir.replimune.com/static-files/ff067885-090d-44ad-89e4-2fa11cf05824

RP2 https://ir.replimune.com/static-files/d96aef73-511b-4cef-9ca1-d5eeba0932d0

Updated corporate presentation (RP1 & RP2 data) https://ir.replimune.com/static-files/1d25b151-d0d9-460d-8fb8-a7b229bf257c

SITC

Title: (650) An Open-label, multicenter, Phase 1/2 clinical trial of RP1, an enhanced potency oncolytic HSV, combined with nivolumab: Updated results from the skin cancer cohorts

Background:
RP1 is an enhanced potency oncolytic HSV encoding a fusogenic protein (GALV-GP R-) and GM-CSF which has previously demonstrated tolerable safety and tumor regression alone and with nivolumab in patients with a number of tumor types. Updated data from the phase 1 expansion with nivolumab, melanoma phase 2 (enrollment complete) and non-melanoma skin cancer (NMSC; enrollment ongoing) cohorts will be presented (NCT03767348). Enrollment of a further 125 patient anti-PD1 refractory cutaneous melanoma cohort; and activation of a cohort of anti-PD1 refractory NSCLC is underway.

Methods:
Stage IIIb-IV melanoma patients for whom anti-PD-1 was indicated or who were refractory to prior anti-PD-1 alone or in combination with anti-CTLA-4, were enrolled. NMSC patients were anti-PD1 naïve. Patients received ≤8 doses of RP1 (≤10 mL/visit Q2W; first dose 106 PFU/mL then 107 PFU/mL) with nivolumab (240 mg IV Q2W for 4 months then 480 mg IV Q4W up to 2 years) from the second RP1 dose.

Results:
As of 24th June 2020, 36 melanoma and 16 NMSC patients had been enrolled with follow up of <1-17 months. Of the melanoma patients, 16 previously antiPD1 treated cutaneous (8 also prior anti-CTLA-4), 8 anti-PD1 naïve cutaneous, 6 mucosal, and 6 uveal. Of the NMSC patients, 10 had squamous cell (CSCC), 3 had a basal cell, 1 had Merkel cell carcinomas, and 2 had angiosarcoma. Treatment emergent adverse events (TEAEs) remain consistent with phase 1, with RP1 side effects generally of Grade 1/2 constitutional-type symptoms, with no exacerbation of the side effects expected for nivolumab. At the data cut-off, 5 previously anti-PD1 treated (4 also anti-CTLA-4) cutaneous melanoma patients, 4 anti-PD1 naïve cutaneous melanoma patients, two mucosal melanoma patients (one anti-PD1 refractory) and one uveal melanoma patient (ipi/nivo refractory) have achieved response (WHO criteria for uveal). For NMSC, for the 13 patients with >8 weeks follow up, one of two angiosarcoma patients and seven of eight CSCC patients (5 CR) have achieved response (CSCC ORR 87.5%; CR rate 62.5%, including of uninjected visceral disease). Tumor biopsies in patients continue to routinely show immune activation, including robust recruitment of CD8+ T cells, reversal of T cell exclusion, and increased PD-L1 expression. Treatment remains ongoing, and current data will be presented.

Conclusions:
RP1 and nivolumab have continued to be well tolerated, with continued promising anti-tumor activity in patients with skin cancers, including those with anti-PD1 refractory and other difficult to treat melanomas, and in patients with CSCC.


Title: (647) Initial results of a phase 1 trial of RP2, a first in class, enhanced potency, anti-CTLA-4 antibody expressing, oncolytic HSV as single agent and combined with nivolumab in patients with solid tumors

Background:
RP2 is an enhanced potency oncolytic HSV-1 expressing granulocytemacrophage colony-stimulating factor (GM-CSF), a fusogenic protein (GALVGP R-), and an anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) antibody-like molecule which is being tested in an open-label, multicenter, phase 1 study alone and combined with PD-1 blockade (NCT04336241).

Methods:
The objectives were to assess initial safety and efficacy and determine the recommended phase 2 dose (RP2D) of RP2 alone and combined with nivolumab. Patients were to be treated using a 3+3 dose escalation at two dose levels of up to 10mL of RP2 Q2W up to 5 times (dose level 1: 105 PFU/mL then 4 doses of 106 PFU/mL; dose level 2: 106 PFU/mL then 4 doses of 107 PFU/mL). Following determination of the RP2D, additional HSV-1 seronegative patients were to be enrolled such that ≥3 had been dosed with RP2 at the RP2D, and a combination cohort of up to 30 patients dosed up to 8 times with RP2 at the RP2D combined with nivolumab (240mg Q2W for 4 months from the second RP2 dose, then 480 mg Q4W for 20 months) opened. Lesions were injected directly or under imaging guidance used for visceral lesions. Tumor biopsies were obtained for biomarker analysis. Viral shedding and antiHSV antibody titers were also monitored.

Results:
Six HSV seropositive patients were enrolled in the dose-escalation phase with primarily Grade 1-2 adverse events, including febrile and other constitutional symptoms, local inflammation, and erythema observed. There were no DLTs requiring dose level expansion. The RP2D was selected as up to 10mL of 106 PFU/mL followed Q2W by multiple doses of 107 PFU/mL. Of the six patients treated with single agent RP2, three (50%) have ongoing partial responses. Objective responses (including in uninjected tumors) were observed in patients with uveal melanoma (prior ipilumumab/nivolumab; extensive liver metastases), mucoepidermoid carcinoma (prior carboplatin/paclitaxel, bicalutamide, ceralasertib), and esophageal cancer (prior durvalumab, M6620, capecitabine, oxaliplatin, cisplatin, chemoradiation; liver and abdominal node metastases). Enrollment is underway in HSV seronegative patients and in combination with nivolumab. Updated data including biomarker and biodistribution data will be presented.

Conclusions:
The Phase 1 clinical data supports the safety and efficacy of single agent P2, including demonstration of uninjected tumor response in patients with difficult to treat advanced cancers. This data supports the hypothesis that anti-CTLA-4 delivered intra-tumorally through oncolytic virus replication, with accompanying antigen release and presentation, can provide potent anti-tumor effects.

https://www.globenewswire.com/news-release/2020/10/14/2108642/0/en/Replimune-Announces-Presentation-at-the-
2020-Society-for-Immunotherapy-of-Cancer-SITC-Annual-Meeting.html

Slides from the IO Summit (the company isn't taking ONCR's shots against its platform lying down) https://ir.replimune.com/static-files/947e0305-23e9-4a5b-916d-9a069ccf9068

Slides from the event https://ir.replimune.com/static-files/def39b44-9f58-4fbd-8a36-2f96f628519a

This came out a few day before https://klendathucapitalist.com/2020/06/02/replimune-the-lost-art-of-immunotherapy/

The company will host a conference call to provide updated data from patients with melanoma and non-melanoma skin cancers treated with RP1 combined with Opdivo in its ongoing PhI/II trial. The investor event will be held on the 3rd https://edge.media-server.com/mmc/p/asqtbief/aud/st/webcast

Some data from ASCO https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.e22050

Looks good https://meetinglibrary.asco.org/record/192615/abstract

Initial data on RP2 could be presented at SITC.

Two new trials listed. The first is a 1b (registration-directed) of RP1 in transplant patients with advanced CSCC (NCT04349436) and the other is a PhI/II testing RP2 +/- Opdivo (NCT04336241).

Small number, but encouraging data on another 'armed' OV*. The full data from cohort one (18 response evaluable patients) should be presented at ASCO. In cohort two they will be testing a triplet (adding Tecentriq). I hope after the PhI RP3 gets tested in a range of 'cold' types, such as pancreatic.

* https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.4_suppl.716

An update from last month https://ir.replimune.com/static-files/7aa0f042-b0cf-4f89-aa58-3f48943f7643

J.P. Morgan webcast https://jpmorgan.metameetings.net/events/hc20/sessions/29931-replimune/webcast

Slides https://ir.replimune.com/static-files/34a367a4-1b90-44b0-9b7a-20b744ac2a24

The company has appointed Jean M. Franchi as CFO. Ms. Franchi has over 30 years of experience in the biotech and life sciences industry of varying sizes and stages in both the U.S. and international markets. Most recently, she served as the CFO for Merrimack Pharma.

Piper Jaffray slides https://ir.replimune.com/static-files/023a7710-3ec0-4f57-a703-99c7351ae413

So the company will raise ~$80M with this PO. This is a discount to the recent ~$17/share, but just a month ago it was ~$12/share. After this closes they will have ~$180-190M to fund the ongoing and planned trials. Also, once the manufacturing facility opens this should save money.

The PR https://markets.businessinsider.com/news/stocks/replimune-presents-initial-clinical-data-with-rp1-that-strongly-supports-expansion-of-clinical-programs-in-melanoma-and-cutaneous-squamous-cell-carcinoma-cscc-1028673120

Poster https://ir.replimune.com/static-files/d8fe8ff4-47ce-4b49-9cea-118b347d79ae

CSCC deck https://ir.replimune.com/static-files/6055ead4-f9f7-496d-bfd5-c2e22b31bd2a

Melanoma deck https://ir.replimune.com/static-files/22e528d6-c3ae-4156-a8db-e8873d9123a4

Event deck https://ir.replimune.com/static-files/9f8d4d33-ef0a-433f-8483-bba680aae25d