On October 14, 2020 Replimune Group Inc. (NASDAQ: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported that data with the Company’s lead product candidate, RP1, along with initial single agent safety and efficacy data with RP2 in advanced solid tumors, will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting being held virtually from November 9-14, 2020 (Press release, Replimune, OCT 14, 2020, View Source [SID1234568479]).

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The abstracts for these presentations appeared briefly and in error on the SITC (Free SITC Whitepaper) website this morning, prior to their intended release on November 9th 2020, and as a result are provided in full below.

Details of Replimune’s poster presentations:

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

Abstract Authors: Mark Middleton, Joseph J. Sacco, Kevin Harrington, Anna Olsson-Brown, Pablo Nenclares, Francesca Aroldi, Suzanne Thomas, Robert S. Coffin, etc.

Presentation times: Wednesday, Nov. 11 from 5:15–5:45 p.m. EST and Friday, Nov. 13 from 4:40–5:10 p.m. EST

Location: Virtual Poster Hall

Full abstract:

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.

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

Abstract Authors: Mark R. Middleton, Francesca Aroldi, Joseph J. Sacco, Mohammed M. Milhem, Brendan D. Curti, Ari M. Vanderwalde, Scott Baum, Adel Samson, Anna C. Pavlick, Jason Alan Chesney, Jiaxin Niu, Terence Duane Rhodes, Tawnya Lynn Bowles, Robert Conry, Anna Olsson-Brown, Douglas Earl Laux, Praveen Bommareddy, Alex Deterding, Robert S. Coffin, Kevin Harrington

Presentation times: Thursday, Nov. 12 from 4:50–5:20 p.m. EST and Saturday, Nov. 14 from 1–1:30 p.m. EST

Location: Virtual Poster Hall

Full abstract:

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.

As well as during the official presentation times, the posters will also be available for virtual viewing throughout the conference via the SITC (Free SITC Whitepaper) annual meeting website, and will be made available on the Company’s website at www.replimune.com.

On October 14, 2020 RayzeBio, Inc. reported a $45M Series A financing to advance the development of its broad pipeline of targeted radiopharmaceuticals (Press release, RayzeBio, OCT 14, 2020, View Source [SID1234568477]). Co-lead investors venBio Partners and Versant Ventures were joined by Samsara BioCapital.

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"The field of radiopharmaceuticals represents one of the most attractive untapped opportunities in oncology," said Ken Song, M.D., President and CEO of RayzeBio. "We have a clear and systematic strategy to tackle this space, including key partnerships and a suite of rationally designed radiopharmaceutical medicines that can meaningfully impact outcomes for cancer patients."

Emerging field of radiopharmaceuticals

Radiation treatment of cancer has been in practice for decades with external delivery of radiation beams as the primary mode of therapy. In contrast, radiopharmaceuticals, which involve the use of therapeutic radioisotopes administered systemically and targeted to tumors, are emerging as an important area in precision oncology.

"The radiopharmaceutical field is reaching a new inflection due to multiple scientific and translational advances as well as recent clinical demonstration of dramatic efficacy. We believe RayzeBio has the potential to generate similar results across multiple precision oncology targets, a feat that no other company has accomplished," said Jerel Davis, Ph.D., Managing Director at Versant and a RayzeBio board member.

Radiopharmaceuticals enable a theranostic approach wherein the same drug conjugate is used for both diagnostic imaging and therapy by switching out the radioisotope. Doctors can directly visualize tumor uptake of the drug in patients prior to determining which patients should proceed with treatment. This provides a significant advantage for radiopharmaceuticals compared with other cancer treatment modalities.

RayzeBio’s differentiated approach

RayzeBio built its pipeline by coordinating across three main areas – target selection, binder selection and isotope selection.

Target selection – Solid tumor targets that have been clinically validated but not yet explored with radiopharmaceuticals were prioritized. This yielded at least 10 promising targets to pursue.
Binder selection – In selecting the molecule type that binds to targets of interest, multiple factors ranging from affinity to tumor penetration and pharmacokinetics were considered. Macrocyclic peptide mimetics were identified as a promising approach and RayzeBio established a partnership with PeptiDream (Tokyo, Japan) for de novo discovery of binders.
Isotope selection – Actinium-225, an alpha-emitting isotope, is the primary nuclear payload for RayzeBio given its potent cell killing and focused energy release to a few cell diameters thereby minimizing damage to surrounding normal tissues. RayzeBio has secured relationships with suppliers of Actinium-225.
"RayzeBio represents the most attractive opportunity in the radiopharmaceutical space given the breadth of its pipeline, its well thought-out plans to design best-in-class drugs, and the fact it is led by a highly driven, experienced and entrepreneurial team," said Aaron Royston, M.D., Managing Partner at venBio.

Expanded team of RayzeBio

In addition to Dr. Song, the management team launching RayzeBio includes Deborah Charych, Ph.D., co-founder and CTO, and a pharma and biotech industry veteran to lead the biology group. The team has extensive industry experience, having contributed to the development and launch of multiple healthcare products as well as billions of dollars of value creation.

The board of directors includes Dr. Davis; Aaron Kantoff, a founding independent board member of RayzeBio and venture partner at Medicxi; Dr. Royston; and Dr. Song. Samsara’s Mike Dybbs, Ph.D., serves as a board observer.

The company has built relationships with the following clinical and scientific initial advisors and is continuing to expand its network as it makes progress on the various programs.

Carolyn Bertozzi, Ph.D. – Professor of Chemical & Systems Biology and Radiology at Stanford University and Investigator of the Howard Hughes Medical Institute
Thomas Hope, M.D. – Associate Professor and Director of Molecular Therapy for the Molecular Imaging and Therapeutics Clinical Section at University of California San Francisco
George Sgouros, Ph.D. – Professor and Director of Radiological Physics Division at Johns Hopkins University
Wolfgang Weber, M.D. – Professor and Director of the Department of Nuclear Medicine at the Technical University of Munich in Germany (TUM)

On October 14, 2020 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer reported that the U.S. Food and Drug Administration ("FDA") has cleared the Company’s Investigational New Drug ("IND") application for 177Lu-omburtamab-DTPA for the treatment of medulloblastoma, which is the most common type of primary brain cancer in children (Press release, Y-mAbs Therapeutics, OCT 14, 2020, View Source [SID1234568471]). Medulloblastomas are invasive, rapidly growing tumors that, unlike most brain tumors, spread through the cerebrospinal fluid and frequently metastasize to different locations along the surface of the brain and spinal cord.

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177Lu-omburtamab-DTPA embodies the Company’s naked omburtamab antibody radiolabeled with lutetium-177, using DTPA to chelate the lutetium radioisotope to the antibody. Lutetium-177 is a beta-emitter with a half-life of 6.7 days and a maximum energy of 0.5 MeV, corresponding to a maximum soft-tissue penetration of approximately 1 mm.

We anticipate that an international multicenter Phase 1/2 clinical trial will be initiated for the screening of pediatric patients with medulloblastoma during the fourth quarter of 2020.

"Based on our clinical experience with 131I-omburtamab for B7-H3 positive brain metastasis, we are excited to see 177Lu-omburtamab-DTPA make its way to the clinic to establish the safety profile and to determine the maximum tolerated dose. In this study, we hope to leverage our clinical experience from treating 27 medulloblastoma patients with 131I-omburtamab, again using indwelling catheters for intracerebroventricular drug delivery," said Thomas Gad, founder, Chairman and President.

Dr. Claus Moller, Chief Executive Officer further notes, "Children with medulloblastoma represent a clear unmet medical need, and we are very pleased to move this product to the clinic. In addition, we have submitted a separate IND for a basket trial in B7-H3 positive CNS/LM cancers in adults to leverage our experience from treating more than 25 adults with 131I-omburtamab. We expect to initiate the study for the first adult patients to be treated with 177Lu-omburtamab-DTPA during the fourth quarter of 2020, and we are genuinely thrilled to widen our clinical reach to include adult indications."

Researchers at Memorial Sloan Kettering ("MSK") developed the omburtamab antibody, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compound and in Y-mAbs.

On October 14, 2020 Perrigo Company plc (NYSE; TASE: PRGO), a leading provider of Quality, Affordable Self-Care Products, reported that it will release its third quarter financial results on Wednesday, November 4, 2020 (Press release, Perrigo Company, OCT 14, 2020, View Source [SID1234568470]). The Company will also host a conference call beginning at 8:00 a.m. (EST).

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The conference call will be available live via webcast to interested parties in the investor relations section of the Perrigo website at View Source or by phone at 888-317-6003, International 412-317-6061, and reference ID # 3180501. A taped replay of the call will be available beginning at approximately 12:00 p.m. (EST) Wednesday, November 4, until midnight Wednesday, November 11, 2020. To listen to the replay, dial 877-344-7529, International 412-317-0088, and use access code 10148815.

On October 14, 2020 Boehringer Ingelheim and Oxford BioTherapeutics Ltd. (OBT) reported they are building on their successful partnership and are establishing a new alliance to discover additional selective targets for strategic cancer indications to deliver first-in-class treatments for cancer patients (Press release, Boehringer Ingelheim, OCT 14, 2020, View Source [SID1234568469]). Boehringer Ingelheim will use OBT’s OGAP platform to identify novel target opportunities for new immunotherapies utilizing their T-cell engager, cancer vaccine and oncolytic virus platforms . This follows the initiation of the first patient dosing in a Phase 1 clinical trial of a bispecific antibody for the treatment of patients with small cell lung carcinoma and other neoplasms, where the target for the bispecific antibody was discovered during the first phase of the partnership.

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"This collaboration with Oxford BioTherapeutics is important for advancing therapeutic modalities that depend upon the identification of unique and specific tumor antigens within our cancer immunology portfolio," said Jonathon Sedgwick, Ph.D., Senior Vice President and Global Head Cancer Immunology & Immune Modulation Research at Boehringer Ingelheim. "We are committed to developing innovative, efficacious and safe treatment options for patients suffering from cancer, and these novel cancer target discoveries are a key step in the development of new potential treatments."

"We view the hopeful discovery of additional tumor targets as further confirmation of the value of our OGAP platform to identify novel targets that can be substrates for innovative new therapies," said Christian Rohlff, Ph.D., Chief Executive Officer of OBT. "OBT’s platforms are designed to discover and validate novel therapeutic targets and we look forward to continuing our partnership with Boehringer Ingelheim to best address difficult-to-treat cancers."

In addition to the programs in the partnership with Boehringer Ingelheim, OBT’s clinical assets have also been enabled through the OGAP discovery platform. Selecting the right target is fundamental for the successful development of a truly first-in-class oncology product. OBT’s platforms are designed to discover novel therapeutic targets and engineer antibodies to those targets, including CAR-T, other T-cell and NK cell-mediated cytotoxicity (ADCC) therapeutics to best address difficult-to-treat cancers. A major differentiator between OBTs discovery platform and other approaches is the retention of the link between individual patient samples through to the design of therapeutic antibodies and diagnostic patient selection tools, increasing the overall successful transition into clinical development.

Financial terms of the expanded agreement are not being disclosed. Under the terms of the agreement, Boehringer Ingelheim is responsible for the development and commercialization of antibody product candidates that interact with the novel targets identified by OGAP. OBT will receive development and regulatory milestone payments and royalties on any future product sales. To date, Boehringer Ingelheim has exercised two options under the first agreement and has selected two therapeutic candidates for further development.

Boehringer Ingelheim Oncology is taking cancer on by leading the science with cancer cell directed agents, immuno-oncology therapies and their combinations to address unmet needs in lung and gastrointestinal cancers. The company invests significantly in early stage research to identify unexplored and undrugged pathways of cancer. Learn more about Boehringer Ingelheim’s innovation in oncology here.