On November 11, 2019 Replimune Group Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported financial results for its second fiscal quarter, ended September 30, 2019, and provided a corporate update (Press release, Replimune, NOV 11, 2019, View Source [SID1234550863]).

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"It has been a very productive and exciting period for Replimune," said Robert Coffin, Ph.D., President and CEO of Replimune. "The highlight was the SITC (Free SITC Whitepaper) 2019 presentation of RP1 clinical data which confirmed the expected mechanism of action, initial safety profile, and evidence of anti-tumor efficacy providing strong support for our ongoing and expanded programs in CSCC and melanoma. Based directly on this data, the decision was taken to conduct a new clinical trial in solid organ transplant patients with CSCC and in melanoma patients who are refractory to prior treatment with anti-PD1 directed therapy. We were also very pleased to have initiated the first clinical trial of our second clinical product candidate, RP2. Overall we are thrilled with Replimune’s progress in the quarter and excited for the future as we continue to execute upon our mission to make our oncolytic immuno-gene therapies a cornerstone of cancer treatment."

Recent Business Highlights and Upcoming Events

RP1 – Presented initial data from the Phase 1/2 clinical trial of RP1 alone and in combination with Opdivo at SITC (Free SITC Whitepaper) 2019. The data presented demonstrated that RP1 used alone and in combination with Opdivo is well tolerated and showed clear anti-tumor efficacy in target tumor types that provides strong support for Replimune’s ongoing and planned development programs in melanoma and CSCC. This clinical trial is being conducted under a clinical trial collaboration and agreement with Bristol Myers Squibb (BMS) for the supply of Opdivo.

RP1 – Initiated the registration-directed Phase 2 clinical trial of RP1 in combination with Libtayo in CSCC. This multi-center, randomized, controlled clinical trial is intended to enroll approximately 240 patients with CSCC. The clinical trial’s primary objective is to compare the response rate following treatment with RP1 in combination with Libtayo to the response rate achieved with Libtayo alone. Libtayo is an FDA-approved anti-PD-1 therapy developed by Regeneron and Sanofi for the treatment of patients with metastatic or locally-advanced CSCC who are not candidates for curative surgery or radiation. This clinical trial is being conducted under the Company’s collaboration agreement with Regeneron, whereby the Company and Regeneron will split equally development and supply costs. Recruitment into this clinical trial is expected to take approximately 18 to 24 months.

RP1 – Recruitment ongoing in the Phase 2 part of the Phase 1/2 trial of RP1 in combination with Opdivo. The Phase 2 part of the clinical trial is currently enrolling 30-patient cohorts of patients with melanoma, non-melanoma skin cancers, metastatic bladder cancer and microsatellite instability high (MSI-H) tumors.

RP1 – New clinical trial planned of RP1 as monotherapy in organ transplant recipients with CSCC. CSCC represents a significant unmet medical need in organ transplant recipients where it is the most prevalent tumor type in a population at higher risk for malignancy in general, and where anti-PD-1 therapy provides a significant risk of rejection of the transplanted organ. The U.S. Food and Drug Administration (FDA) has accepted the protocol for this clinical trial under the Company’s previously accepted Investigational New Drug Application for RP1. The clinical trial is intended to enroll approximately 30 patients and assess the safety and efficacy of RP1 in liver and kidney transplant recipients with recurrent CSCC. Replimune expects to initiate the clinical trial in the first quarter of 2020.

RP1 – Additional clinical trial intended of RP1 in combination with an anti-PD-1 therapy in anti-PD-1 refractory melanoma patients. Based on the clinical efficacy data to date with RP1 in melanoma, the Company has decided to conduct a new clinical trial of RP1 in combination with an anti-PD-1 therapy in anti-PD-1 refectory melanoma patients. Discussions are underway to determine the particular anti-PD-1 therapy to be used. The trial is expected to begin enrollment in 2020.

RP2 – Initiation of the Phase 1 clinical trial of RP2 alone and in combination with Opdivo. RP2 is based on RP1 but additionally expresses a genetically encoded anti-CTLA-4 antibody-like molecule. The addition of anti-CTLA-4 is intended to block the inhibition of the initiation of immune responses otherwise caused by CTLA-4. The clinical trial is designed to assess the safety, tolerability and to determine the optimal dose of RP2 alone and in combination with Opdivo and is being conducted under a clinical trial collaboration and agreement with BMS for the supply of Opdivo.

RP3 – The Phase 1 clinical trial of RP3 alone and in combination with an anti-PD1 therapy remains on track to initiate in 2020. RP3 is a further armed oncolytic immuno-gene therapy which expresses two immune co-stimulatory activating ligands (CD40L and 4-1BBL) in addition to the GALV-GP R- fusogenic protein and anti-CTLA-4.

Build-out of Replimune’s manufacturing facility to support late-stage development and commercialization remains on schedule. The 63,000-square-foot facility in Framingham, MA is intended to provide multi-product manufacturing capabilities for Replimune’s Immulytic product candidates. The capacity of this facility will be sufficient to support full commercialization of the Company’s product candidates. An occupancy certificate for the facility has been obtained and technology transfer is underway.
Financial Highlights

Replimune reported a net loss of $11.1 million for the quarter ended September 30, 2019 compared with $6.5 million for the same period in the prior year.

Research and development expenses for the quarter ended September 30, 2019 were $8.2 million compared with $5.0 million for the same period in the prior year. The increase in research and development expenses was primarily driven by additional costs related to Replimune’s preclinical and clinical development activities for its pipeline.

General and administrative expenses for the quarter ended September 30, 2019 were $4.1 million compared with $2.1 million for the same period in the prior year. The increase in general and administrative expenses was primarily due to an increase in employee headcount, professional fees and facility costs.

Replimune ended the quarter with $109.9 million in cash, cash equivalents, and short-term investments, compared with $134.8 million as of March 31, 2019.

Based on its current operating plan, Replimune expects that its current cash, cash equivalents, and short-term investments will enable it to fund its operating expenses and capital expenditure requirements into the second half of calendar year 2021.

On November 11, 2019 IBM (NYSE: IBM), American Cancer Society (ACS), the National Comprehensive Cancer Network (NCCN) and the Clinton Health Access Initiative (CHAI), reported a new alliance to help improve access to high-quality cancer care and treatment in Sub-Saharan Africa called Allied Against Cancer (Press release, IBM – Initiate Systems, NOV 11, 2019, View Source [SID1234550879]). The Alliance will support a network of African oncology experts and technical assistance partners to help improve the quality of cancer care, including collaborating closely with the African Cancer Coalition to establish priorities and execute these initiatives locally.

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There are more than 800,000 new cancer cases each year in Sub-Saharan Africa and incidence is projected to double by 2040. And as these countries address the growing cancer epidemic, data and emerging technologies can play a significant role in cancer treatment control and care. The need for more affordable cancer treatment and strong systems for their delivery are crucial to help improve patients’ survival.

To address gaps in access to cancer medicines, ACS and CHAI teamed up in 2016 to bring lower prices for 16 common chemotherapy drugs to a half-dozen countries in Sub-Saharan Africa. And top American oncologists have supported the African Cancer Coalition — comprising of 110 African oncologists representing 34 hospitals from 13 countries in Sub-Saharan Africa—to adapt cancer-treatment guidelines for use in African hospitals. The African Cancer Coalition, working with experts from NCCN, adapted the 46 NCCN Guidelines and NCCN Framework for Resource Stratification of NCCN Guidelines (NCCN Framework) to create the NCCN Harmonized Guidelines for Sub-Saharan Africa specifically to be used by oncologists across Sub-Saharan Africa. These guidelines have been endorsed by leading cancer centers or health ministries in six countries to date.

IBM then developed an online tool called Cancer Guidelines Navigator to provide African oncology professionals with interactive access to the NCCN Harmonized Guidelines for Sub-Saharan Africa at no charge. Oncologists based in Sub Saharan Africa can input a clinical description for a cancer patient1 — such as tumor type, stage, biomarker status, and prior treatments — into the online tool. The Cancer Guidelines Navigator then points the user to relevant treatment options input from the NCCN Harmonized Guidelines. At this time, the tool includes NCCN Harmonized Guidelines for cervical cancer, prostate cancer, breast cancer, diffuse large B-cell lymphoma, and Kaposi sarcoma.

IBM also helped to transform the ACS ChemoSafe Facility Assessment Tool – from an Excel-based document to an interactive, easy to use mobile application- to scale the program’s goal of improving the safety and quality for chemotherapy handling in cancer centers. This tool, which is accessible at no cost on iOS or Android mobile phones or tablets, allows healthcare workers to review the safety of hazardous drugs at each location where they may be handled in their healthcare facility, including the pharmacy receiving, treatment areas, housekeeping, and waste area. Upon completion of the assessment, the tool provides recommendations to help improve the handling of hazardous drugs at potential points of exposure, based on international and national standards. This information may be used by hospitals to create policies and budgets supporting quality improvement.

"Allied Against Cancer brings together a group of top-notch experts to tackle the growing burden of cancer in Africa, and the American Cancer Society is proud to be a founding member of the alliance," said Gary Reedy, Chief Executive Officer, American Cancer Society.

"With the increasing burden of cancer in this part of the world, we must strive to improve patients’ access to timely and affordable care. Technology and data can help create efficient healthcare systems so that national and regional medical networks can increase support their local communities," said Dr. Solomon Assefa, Vice President, Africa & Emerging Market Solutions and Director, IBM Research – Africa.

"These evidence and expert consensus-based treatment recommendations combine the practical with the aspirational, to elevate the quality of cancer care at a time when the people of Sub-Saharan Africa need it most," said Robert W. Carlson, MD, Chief Executive Officer, NCCN.

"This new alliance will help ensure that lifesaving medications and tools are available where and when they are needed so that health professionals can better diagnose, treat, and care for patients suffering with cancer throughout Sub-Saharan Africa," said CHAI CEO Ira C. Magaziner.

"To address the growing burden of cancer in Africa and worldwide, African oncologists need quick and easy access to current treatment options as well as quality, affordable treatment for their patients. This alliance provides an opportunity to strengthen the ties within the global oncology community in ways that can deliver better outcomes for our patients," said Professor Isaac Adewole, Co-chair of the African Cancer Coalition.

On November 10, 2019 Stone Capital and Biosyngen reported have partnered to establish a Biopharmaceutical Investment Fund in Singapore, the signing ceremony was held in Ascendas One Hub of Sino-Singapore Guangzhou Knowledge City (Press release, Stone Biostatistics, NOV 10, 2019, View Source [SID1234550834]). The key investment targets of the biopharmaceutical fund of US$50 million raised is for Biosyngen biopharmaceutical technology transfer platform and to incubate companies.

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Biosyngen has been an angel investment platform for biopharmaceutical projects, who has formed projects with selected early stage technologies after stringent screening process. This fund allows Biosyngen to take advantage of Singapore pool of talent, technology, regulations, government support and other industrial resources, in particular cell therapy technologies, Biosyngen provides high-efficient incubation support and clinical transformation of the projects. The Company is also taking advantage of the Chinese government’s policy support, environment and the rich clinical trial resources in China. When the projects reach certain level of maturity, they will be further developed and commercialised in China and ASEAN, thereby meeting the needs of both markets.

Mr. Wang Liqun, Chairman of Stone Capital and Director of Biosyngen; Dr. Victor Li Lietao, Founder and CEO of Biosyngen,; and Mr. Wang Shuli, Chairman of Biosyngen attended the event to witness a milestone in the progress of the company. As a well-known successful investor, Mr. Wang expressed his appreciation for Biosyngen on the competency of project transformation over the past three years. He also generously shared his management experience and made suggestions to Dr. Li. Dr. Li expressed his sincere gratitude to Mr. Wang for coming onboard Biosyngen as a Director as this will enhance the function of Biosygnen biopharmaceutical technology transfer platform which will accelerate the business development of Biosyngen.

On November 9, 2019 Bolt Biotherapeutics, Inc., a private biotechnology company focused on using its Immune-Stimulating Antibody Conjugate (ISAC) platform technology to unleash the power of the immune system to treat cancer, reported new preclinical data demonstrating profound antitumor efficacy for its lead HER2 ISAC therapeutic program, when administered as a monotherapy, resulting in the complete eradication of large tumors (Press release, Bolt Biotherapeutics, NOV 9, 2019, View Source [SID1234550864]). The poster presentation entitled "HER2-targeting TLR7/8 immune-stimulating antibody conjugates elicit robust myeloid activation and anti-tumor immune responses in a TLR- and FcR- dependent manner" was presented at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in National Harbor, Maryland.

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"These exciting preclinical data provide a strong rationale for moving our ISAC cancer immunotherapy platform into clinical testing and I’m pleased to report that we expect to initiate our first clinical trial for our HER2 monotherapy in early 2020," stated Randall Schatzman, Ph.D., chief executive officer of Bolt. "While much progress has been made in cancer immunotherapy, there still remains a significant need for single-agent therapies that can impact well-established tumors and provide durable efficacy in tumors that are refractory to standard of care therapies. Our proprietary Boltbody ISACs embody all of these components, and we are highly optimistic about the future of this platform to impact cancer."

"We believe such profound antitumor activity is unprecedented, including complete tumor eradication in large tumors, with an immunotherapeutic systemically administered as a monotherapy," stated David Dornan, Ph.D., senior vice president of research at Bolt Biotherapeutics. "Our data define the details of the mechanism of action by which our Boltbody technology is able to eliminate these hard to treat solid tumors, while generating immunological memory to suppress recurrence."

In the series of studies presented at SITC (Free SITC Whitepaper), key preclinical data show:

ISAC antitumor activity requires tumor target expression, interaction with Fc gamma receptors on immune cells, and TLR7/8 engagement
Single-agent anti-HER2 ISAC treatment led to in vivo tumor regression and clearance in models with large tumor burden and are resistant to anti-HER2 naked antibody treatment
Immunological memory was achieved as measured by protection from subsequent tumor growth. In syngeneic tumor models in which anti-HER2 ISAC treatment led to tumor clearance, hosts that were re-challenged with the parental tumor cell line lacking HER2 antigen expression were resistant to tumor growth. This protection was mediated by T cells as evidenced by the ability to re-establish tumors after the deletion of CD4 and CD8 T cells.
About Bolt Biotherapeutics’ Immune-Stimulating Antibody Conjugate (ISAC) Platform Technology
The Boltbody platform consists of Immune-Stimulating Antibody Conjugates (ISAC) that harness the ability of innate immune agonists to convert cold tumors into immunologically hot tumors thereby illuminating tumors to the immune system and allowing them to be invaded by tumor killing cells. Boltbody ISACs have demonstrated the ability to eliminate tumors following systemic administration in preclinical models and have also led to the development of immunological memory, which is predicted to translate into more durable clinical responses for patients.

On November 9, 2019 Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer, and other indications, reported the presentation of data from the phase 1 dose-escalation monotherapy study of PRS-343, a 4-1BB/HER2 bispecific for the treatment of HER2-positive solid tumors, in a late-breaking oral presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting. PRS-343 demonstrated single-agent anti-tumor activity, including partial responses, in heavily pre-treated patients across multiple HER2-positive tumors (Press release, Pieris Pharmaceuticals, NOV 9, 2019, View Source [SID1234550812]). Beyond demonstrating clinical benefit, PRS-343 showed a potent increase in CD8+ T cell numbers and proliferative index in the tumor microenvironment of responders, indicative of 4-1BB agonism on T cells. PRS-343 was safe and well tolerated at all doses and schedules tested.

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"The data presented today demonstrate PRS-343’s potential to make a meaningful difference for patients with tumors that are difficult to treat with currently-available therapies," said Geoffrey Y. Ku, medical oncologist at Memorial Sloan Kettering and the principal investigator for the PRS-343 monotherapy trial. "Beyond today’s presentation, I look forward to sharing some of these case studies at Pieris’ upcoming R&D day alongside emerging data from the study of PRS-343 in combination with atezolizumab."

The ongoing phase 1 first-in-human, open-label multicenter trial has enrolled 53 patients, including 19 patients with gastric cancer, 14 patients with breast cancer, 6 patients with gynecological cancers, and 14 patients with other tumor types. Eleven dose cohorts have been evaluated at a Q3W dosing schedule, with the 11th dose level (8 mg/kg) also being evaluated at a Q2W dosing schedule. Pre- and post- treatment biopsies were obtained from many of the patients. Trial objectives include evaluation of safety and tolerability, characterizing the pharmacokinetic profile, assessing pharmacodynamic and potential immunogenicity effects, and investigating clinical response.

As of the cut-off date of October 23, 2019, 18 patients were evaluable for a response at active dose levels, which began at cohort 9 (2.5 mg/kg).

At the 8 mg/kg Q2W dose level, one patient with stage 4 gastric adenocarcinoma and one patient with stage 4 gynecological carcinoma achieved confirmed partial responses; the remaining patients experienced stable disease, for an overall disease control rate of 100% in this cohort as best response.
Across the remaining active dose levels and schedules, an additional five patients experienced stable disease.
Biomarker data from post-treatment tumor biopsies in patients receiving active dose levels and showing clinical benefit reflected a pronounced increase in CD8+ T cell numbers.
As of the cutoff date, treatment duration across active dose levels is over 30 weeks.
Treatment-related adverse events (AEs) were primarily grade 1 and 2. The most common AEs were infusion related reactions and fatigue. No patients experienced a dose-limiting toxicity and a maximum tolerated dose has not been reached.
"In addition to being the first 4-1BB bispecific to enter the clinic, PRS-343 is our lead immuno-oncology asset, and we believe this dataset serves as early clinical validation of our 4-1BB-targeting immuno-oncology approach and the Anticalin bispecific platform," said Stephen S. Yoder, President and Chief Executive Officer of Pieris. "PRS-343 shows promising signs of efficacy linked to clear biomarker evidence of 4-1BB agonism, in addition to being safe and well tolerated. We look forward to concluding this escalation trial in the near term and initiating an expansion trial informed by the emerging data. We also look forward to initiating clinical development of our 4-1BB/PD-L1 bispecific, PRS-344, with Servier in the first half of next year."