On October 6, 2022 Knight Therapeutics Inc., (TSX: GUD) ("Knight") a pan-American (ex-USA) specialty pharmaceutical company, reported that its Brazilian affiliate, United Medical Ltd., has submitted a marketing authorization application for tafasitamab in combination with lenalidomide to ANVISA, the Brazilian health regulatory agency, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT) (Press release, Knight Therapeutics, OCT 6, 2022, View Source [SID1234621837]).

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In September 2021, Knight entered into an exclusive supply and distribution agreement with Incyte (NASDAQ:INCY), for the exclusive rights to distribute tafasitamab (sold as Monjuvi in the United States and Minjuvi in Europe), as well as pemigatinib (Pemazyre), in Latin America.

"We are delighted to reach this key milestone for tafasitamab in Brazil," said Samira Sakhia, President and Chief Executive Officer of Knight Therapeutics. "Upon approval, combination therapy with tafasitamab and lenalidomide will be an important new therapeutic option for eligible patients with relapsed or refractory DLBCL in Brazil. We look forward to continuing to work with the support of our partner, Incyte, as we work towards regulatory submissions in additional countries in Latin America over the next year."

About Tafasitamab

Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting immunotherapy. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) and Antibody-Dependent Cellular Phagocytosis (ADCP).

In the United States, Monjuvi (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplantation (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In Europe, Minjuvi (tafasitamab) received conditional approval, in combination with lenalidomide, followed by Minjuvi monotherapy, for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who are not eligible for autologous stem cell transplantation (ASCT).

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in several ongoing combination trials.

Minjuvi and Monjuvi are registered trademarks of MorphoSys AG. Tafasitamab is co-marketed by Incyte and MorphoSys under the brand name Monjuvi in the U.S., and marketed by Incyte under the brand name Minjuvi in Region Europe, the United Kingdom and Canada. As part of its agreement with MorphoSys, Incyte received exclusive commercialization rights for tafasitamab outside the United States.

XmAb is a registered trademark of Xencor, Inc.

On October 6, 2022 T-Cure Bioscience, Inc., a privately held company focused on developing T cell receptor (TCR) therapy products for the treatment of solid tumors, reported that the National Cancer Institute (NCI) and Rutgers University sites are open to recruit patients for the treatment of Kita-Kyushu lung cancer antigen 1 (KK-LC-1) expressing malignancies, including gastric, lung, cervical and triple negative breast cancers (Press release, T-Cure Bioscience, OCT 6, 2022, View Source [SID1234621836]). The investigator-initiated phase 1 trials are intended to evaluate the safety and tolerability with dose escalation of the autologous TCR-T cells targeting KK-LC-1. The investigators are now actively recruiting participants who have failed first-line therapy for the above-referenced solid tumors.

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T-Cure licensed the commercial rights of the KK-LC-1 TCR-T therapy and entered into a Cooperative Research and Development Agreement (CRADA) with the NCI in 2020. The Company also initiated pre-clinical and clinical studies on KK-LC-1 TCR-T with Rutgers University in 2021.

"We have been working with the principal investigator at Rutgers University, Dr. Christian Hinrichs, and the NCI, Drs. James Gulley and Scott Norberg for a couple of years. We are extremely excited to see both sites have received IND clearance from the FDA, and are now open for recruitment", stated Gang Zeng, Ph.D., Chief Executive Officer of T-Cure. "Our investigators are key opinion leaders of the cell therapy field. We are fortunate to work together to advance this novel TCR product candidate through the first ever clinical development in the world."

Patients entering the trial are selected based on their expression of the KK-LC-1 antigen as determined by an immunohistochemistry assay. This assay was developed by T-Cure and validated for use in the ongoing trials.

Of note, the KK-LC-1 TCR was isolated from the tumor-infiltrating lymphocytes of a patient who had a complete response to immunotherapy without any toxicities. KK-LC-1 is a unique target and cannot be readily targeted by antibody, chimeric antigen receptor (CAR), or antibody drug conjugate (ADC) therapies. Trials at Rutgers University and NCI (clinicaltrials.gov link) are first-in-human targeting KK-LC-1 for multiple solid tumors.

On October 6, 2022 Sanofi US reported it has entered into a co-promotion service agreement with Provention Bio, Inc., for the commercialization of teplizumab in the United States (Press release, Sanofi, OCT 6, 2022, View Source [SID1234621812]). Teplizumab, developed by Provention, is an investigational anti-CD3 monoclonal antibody that is being evaluated for the delay of clinical type 1 diabetes (T1D) in at-risk individuals, as indicated by the presence of two or more T1D-related autoantibodies. If approved by the U.S. Food and Drug Administration (FDA), teplizumab would be the first-ever disease-modifying therapy in T1D.

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Pending FDA approval, Sanofi US will co-promote teplizumab along with its existing portfolio of diabetes therapies, and leverage its customer-facing field teams with the aim of accelerating uptake of teplizumab across the U.S.

Olivier Bogillot
Head of U.S. General Medicines, Sanofi
"We are delighted by the prospect of supporting Provention Bio in bringing to the U.S. what could become the first-in-class therapy to change the course of type 1 diabetes. If approved, Sanofi US will leverage our existing world-class capabilities in diabetes care to enhance efforts in both patient and healthcare provider access. We are prepared to tap into all of our internal expertise to support the successful launch of this innovative therapy."

Jason Hoitt
Chief Commercial Officer, Provention Bio
"Teplizumab represents a potentially disruptive new therapy for T1D, and we are excited to work alongside Sanofi US to bring the first-ever disease-modifying therapy, if approved, to individuals in the U.S. who are at risk of developing clinical-stage type 1 diabetes."

The FDA is expected to make a decision on the regulatory approval for teplizumab on November 17, 2022.

Agreement Terms
Dependent on a positive decision from the FDA, Provention Bio will contract Sanofi US customer-facing field teams. Provention Bio retains all rights to teplizumab, responsible for key activities such as R&D, pharmacovigilance, production, quality and safety.

As of the effective date of the service agreement, Sanofi US has committed to make an upfront payment of $20 million to Provention Bio. In connection with this transaction, Provention Bio has granted Sanofi US an exclusive right of first negotiation for a potential in-license agreement of teplizumab in T1D.

Sanofi US also has agreed to make an equity investment of $35 million in Provention Bio, within a defined period after FDA approval of teplizumab, should this take place.

About type 1 diabetes
Type 1 diabetes is a condition caused by autoimmune damage of the insulin-producing beta-cells of the pancreas. As a result of this autoimmune attack, the body produces very little or no insulin which can lead to death if the insulin is not replaced.

Living with T1D is complex. In addition to daily insulin injections or infusion via an insulin pump, people living with T1D also need to adopt a strict management plan which includes regular blood sugar monitoring, healthy diet and physical activity.

On October 6, 2022 EpicentRx, a late clinical stage biopharmaceutical company with novel therapies to target cancer and inflammatory diseases, reported the start of dosing in China for the global Phase 3 clinical trial REPLATINUM (NCT05566041) with partner SciClone Pharmaceuticals (Press release, EpicentRx, OCT 6, 2022, View Source [SID1234621809]). The trial in the US and China is designed to compare the efficacy of RRx-001 and a first line platinum doublet versus a platinum doublet in approximately 300 third-line or beyond extensive stage SCLC patients that previously received a platinum doublet and a checkpoint inhibitor.

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RRx-001, a tumor-activated small molecule that inhibits the NLRP3 inflammasome and repolarizes tumor associated macrophages (TAMs), is used to restore sensitivity to chemotherapy that has already been tried. The primary endpoints of the study are progression free survival (PFS) and overall survival (OS) in patients with third line and beyond extensive stage SCLC.

The goal is to evaluate the efficacy of platinum doublet rechallenge after treatment with RRx-001 in late line extensive stage SCLC, a stubbornly resistant cancer with a nearly one-hundred percent mortality rate. To date, RRx-001 has not been associated with any dose limiting toxicities either alone or in combination with chemotherapy.

"The deck is stacked against patients with SCLC, a highly aggressive and metastatic cancer. These patients are usually heavy smokers with underlying smoking related issues such as chronic cardiovascular disease, end-stage renal failure, diabetes, and COPD. The best responses are seen in first line with platinum-based chemotherapy, but resistance develops quickly, and later line options are few and far between. RRx-001 is a chemosensitizer with the potential to help SCLC patients around the world by restoring sensitivity to first line platinum-based chemotherapy," said Dr. Tony R. Reid, CEO of EpicentRx.

EpicentRx and SciClone Pharmaceuticals established a licensing agreement for RRx-001 in Greater China in 2020.

The Phase 3 trial follows the successful completion of the Phase 2 QUADRUPLE THREAT clinical trial (NCT02489903) of RRx-001 in late line SCLC patients, which achieved its primary endpoint, meeting criteria to begin REPLATINUM.

About RRx-001
RRx-001 is an only-in-class investigational NLRP3 inhibitor with dual anti-inflammatory and anticancer activity for the treatment of multiple conditions in oncology, gastroenterology, autoimmunity, and neurodegeneration. It impairs tumor growth in multiple cancer models, reprograms myeloid compartments, and reverses resistance to previously administered chemotherapy. Its dual mechanism of action—protection of normal tissues and toxicity to tumors—is related to the molecular fragmentation that occurs only in the interior of tumors, where tumor associated macrophages (TAMs) are located. Increased infiltration of TAMs, a sine qua non for the anticancer activity of RRx-001, has been observed in many tumors including SCLC. For more information on the Phase 3 trial, please visit View Source

On October 6, 2022 Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a pioneer in computational target discovery, reported that it will present new clinical data from its dual combination COM701/nivolumab MSS-CRC cohort expansion study and research data on the differentiation of PVRIG from other immune checkpoints in two oral presentations at the 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place between 10-12 November 2022, Boston, MA (Press release, Compugen, OCT 6, 2022, View Source [SID1234621808]).

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Oral presentation details:

Title: COM701 plus nivolumab demonstrates preliminary antitumor activity and immune modulation of tumor microenvironment in patients with metastatic MSS-CRC and liver metastases

Abstract Number: 659

Session Title: Clinical Development of Novel Checkpoint Inhibitors

Session Date Thursday, November 10, 2022, 6:45pm ET

Title: PVRIG, a novel T cell checkpoint, is preferentially expressed in TLS on stem-like memory T cells, potentially inhibiting their expansion

Abstract Number: 504

Session Title: Next Generation Checkpoint Blockade: Mechanisms of Action

Session Date: Friday, November 11, 2022, 5:20pm ET

Compugen’s presentations will be available on the publications section of Compugen’s website, www.cgen.com following presentation.