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PDS Biotech Reports Median Overall Survival (OS) of 21 Months in Advanced, Refractory Cancer Patients Having Few Remaining Treatment Options and with Reported Historical Survival of 3-4 months

On December 28, 2022 PDS Biotechnology Corporation (Nasdaq: PDSB), a clinical-stage immunotherapy company developing a growing pipeline of targeted immunotherapies for cancer and infectious disease, reported expanded interim data in a Phase 2 clinical trial investigating the PDS0101-based triple combination therapy in advanced human papillomavirus (HPV)-positive cancers (Press release, PDS Biotechnology, DEC 28, 2022, View Source [SID1234625644]). The triple combination of PDS0101 with the tumor-targeting IL-12 fusion protein M9241 (formerly known as NHS-IL12), and bintrafusp alfa, a bifunctional fusion protein targeting two independent immunosuppressive pathways (PD-L1 and TGF-β), is being studied in CPI-naïve and CPI-refractory patients with advanced HPV-positive anal, cervical, head and neck, vaginal, and vulvar cancers.

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The triple combination Phase 2 trial (NCT04287868) is being conducted at the Center for Cancer Research (CCR) at the National Cancer Institute (NCI), one of the Institutes of the National Institutes of Health.

All patients in the study had failed prior treatment with chemotherapy and 90% had failed radiation treatment. The interim efficacy data (n=50) involves 37 HPV16-positive evaluable patients, including 29 patients who have, in addition, failed treatment with CPIs (CPI refractory). Highlights of the expanded interim data are as follows and are consistent with the results presented at American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2022 and prior interim data announced in October:

Median OS is 21 months in 29 checkpoint inhibitor refractory patients who received the triple combination. The reported historical median OS in patients with CPI refractory disease is 3-4 months.

In CPI naïve subjects, 75% remain alive at a median follow-up of 27 months. As a result, median OS has not yet been reached. Historically median OS for similar patients with platinum experienced CPI naïve disease is 7-11 months.

Objective response rate (ORR) in CPI refractory patients who received the optimal dose of the triple combination is 63% (5/8). In current approaches ORR is reported to be less than 10%.

ORR in CPI naïve patients with the triple combination is 88%. In current approaches ORR is reported to be less than 25% with FDA-approved CPIs in HPV-associated cancers.

Safety data have not changed since October’s update. 48% (24/50) of patients experienced Grade 3 (moderate) treatment-related adverse events (AEs), and 4% (2/50) patients experienced Grade 4 (severe) AEs, compared with approximately 70% of patients receiving the combination of CPIs and chemotherapy reporting Grade 3 and higher treatment-related AEs.

"The expanded data continue to demonstrate the durability and tolerability of the PDS0101-based triple combination therapy in advanced HPV-positive cancers, an extremely challenging population of refractory and previously untreatable HPV-positive patients," stated Dr. Frank Bedu-Addo, President and Chief Executive Officer of PDS Biotech. "We are pleased to see the continued consistency in the data with each update and we look forward to meeting with the FDA to discuss the registrational pathway."

Both M9241 and bintrafusp alfa are owned by Merck KGaA, Darmstadt, Germany, and its affiliates.

NCI clinical trial leads to atezolizumab approval for advanced alveolar soft part sarcoma

On December 28, 2022 A clinical trial led by the National Cancer Institute (NCI), part of the National Institutes of Health, reported the first approval of a treatment for advanced alveolar soft part sarcoma (ASPS) (Press release, US NCI, DEC 28, 2022, View Source [SID1234625643]). The immunotherapy drug atezolizumab (Tecentriq) was recently approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults and children 2 years and older with ASPS that has spread to other parts of the body or cannot be removed by surgery.

ASPS is an extremely rare cancer that affects mostly adolescents and young adults. The approval was based on data from a non-randomized phase 2 trial (NCT03141684) funded by NCI and led by Dr. Alice Chen, M.D., of the Developmental Therapeutics Clinic in NCI’s Division of Cancer Treatment and Diagnosis (DCTD). Genentech, a member of the Roche Group and the manufacturer of atezolizumab, provided the drug to NCI through a cooperative research and development agreement. The results of the study are being prepared for publication.

"Forty percent of the patients were treated at the NIH Clinical Center in Bethesda," said James H. Doroshow, M.D., director of DCTD. "Our ability to bring patients in from all over the world was a key factor in the ability to do the study."

"This approval will make a huge impact in terms of a rare disease that has been particularly challenging to treat," Dr. Chen noted.

This is the largest study on ASPS. It is also the first study conducted in the NCI-funded Experimental Therapeutics Clinical Trials Network that has resulted in a drug approval. The network enabled sarcoma specialists at academic medical centers from across North America to enroll patients in the trial.

"This is a major milestone for investigators in the Experimental Therapeutics Clinical Trials Network, as well as for the ASPS patient community, and for research on rare cancers," said Elad Sharon, M.D., of DCTD, who is one of the study leaders.

This is also the first time atezolizumab has been approved for children. Dr. Chen noted that this was enabled by the participation of the Pediatric Oncology Branch in NCI’s Center for Cancer Research, which helped enroll children in the trial.

"This study is an important example of collaboration between pediatric and medical oncology, allowing children with very rare cancers access to effective new therapies," said John W. Glod, M.D., Ph.D., of the Pediatric Oncology Branch. "The entire study team is grateful to the patients who participated in the study and made this work possible."

About 80 people in the United States are diagnosed with ASPS every year. The disease typically begins in the soft tissue that connects and surrounds the organs and other tissues. Although the disease grows slowly, once it spreads it is often deadly, and chemotherapy is ineffective. About 50% of patients with metastatic disease are still alive after five years. New targeted treatments, including drugs called tyrosine kinase inhibitors, do not have lasting effectiveness. Recently, however, immunotherapy drugs have shown promise as possible therapies for ASPS.

Atezolizumab is an anti-PD-L1 immune checkpoint inhibitor that works by helping the immune system respond more strongly to cancer. FDA has approved atezolizumab for the treatment of patients with several cancer types, including liver cancer, melanoma, and lung cancer.

In 2020, FDA granted breakthrough therapy designation for atezolizumab to treat patients with unresectable or metastatic ASPS. This designation means that atezolizumab, which is intended to treat a serious condition, had met FDA’s criteria for expedited development and review of the drug. Later that year, FDA granted orphan drug designation to atezolizumab for soft tissue sarcoma in general. This status provides incentives for companies to develop a drug for rare diseases.

The phase 2 trial enrolled 49 ethnically diverse patients ages 2 and older with metastatic ASPS, who were given an infusion of atezolizumab every 21 days. About a third of the patients responded to the treatment with some degree of tumor shrinkage, according to their doctor’s assessment. Most of the other patients experienced stable disease.

After two years of treatment, patients were given the opportunity to stop treatment and go on a treatment break for up to two years with close monitoring. None of the patients who took a treatment break had disease progression during that time.

Serious side effects occurred in 41% of patients receiving atezolizumab; these included anemia, diarrhea, rash, dizziness, hyperglycemia, and pain in the extremities. However, no patients came off the study because of side effects.

"This approval represents a victory for rare diseases, which are understudied in clinical trials," said Dr. Chen. "For this approval to go through in a rare disease, and to be able to make an impact on these young people’s lives, is very significant."

Research teams are now conducting additional trials with atezolizumab for patients with ASPS, including giving the drug in combination with other therapies.

Nexcella, Inc., a subsidiary of Immix Biopharma, announces poster presentation at the European Society for Blood and Marrow Transplantation and European Hematology Association 5th Annual European CAR T-cell Meeting

On December 28, 2022 Nexcella, Inc., a subsidiary of Immix Biopharma, Inc. (Nasdaq: IMMX) ("ImmixBio", "Company", "We" or "Us") reported that updated NXC-201 clinical data has been selected to be presented at the upcoming European Society for Blood and Marrow Transplantation and European Hematology Association (EHA) (Free EHA Whitepaper) 5th Annual European CAR T-cell Meeting to be held in Rotterdam, Netherlands February 9-11, 2023 (Press release, Immix Biopharma, DEC 28, 2022, View Source [SID1234625641]).

"We are delighted to be presenting additional clinical data at the upcoming at European Society for Blood and Marrow Transplantation and European Hematology Association (EHA) (Free EHA Whitepaper) 5th Annual European CAR T-cell Meeting," said Polina Stepensky, MD, Director of the Hadassah Medical Organization’s Department of Bone Marrow Transplantation and Immunotherapy for Adults and Children, and principal study investigator. "As we continue to accumulate clinical data, we are learning more about the potential for this therapy to treat multiple myeloma and AL amyloidosis."

Posters to be presented:

"Point-of-care CART manufacture and delivery for the treatment of multiple myeloma and AL amyloidosis: the experience of Hadassah Medical Center"
Nexcella, Inc. previously announced that NXC-201 (formerly HBI0101) produced 85% overall response rate (ORR) and 71% complete response/stringent complete response (CR/sCR) at the therapeutic dose from the first 20 patients in an ongoing phase 1b/2a relapsed/refractory multiple myeloma ongoing clinical trial as of the June 27, 2022 data cutoff with a median of 6 (range, 3-13) prior lines of therapy. NXC-201 also produced 100% ORR and 100% organ response rate in 4 relapsed/refractory AL Amyloidosis patients as of the February 26, 2022 AL Amyloidosis manuscript publication date. In addition, zero neurotoxicity of any grade was observed and zero events of immune effector cell-associated neurotoxicity syndrome (ICANs) were observed with NXC-201 treatment. These data were published in Haematologica View Source (multiple myeloma) and Clinical Cancer Research View Source (AL amyloidosis).

Low-grade (grade 1/2) CRS duration of median 2 days with median onset of 1-day post-dosing (range, 1-5 days) at therapeutic dose in relapsed/refractory multiple myeloma points to NXC-201 potentially becoming the first and only out-patient CAR-T for Multiple Myeloma, AL Amyloidosis and other BCMA-positive malignancies.

About NEXICART-1

NEXICART-1 (NCT04720313) is an ongoing Phase 1b/2, open-label study evaluating the safety and efficacy of NXC-201 (formerly HBI0101), in adults with relapsed or refractory multiple myeloma, all of which as of June 27, 2022 were triple-class refractory (to at least 1 immunomodulatory drug, 1 proteasome inhibitor and 1 anti-CD38 antibody).

The primary objective of the Phase 1b portion of the study, is to characterize the safety and confirm the Maximally Tolerated Dose (MTD) and Phase 2 dose of NXC-201. The Phase 2 portion of the study will evaluate the efficacy and safety of NXC-201 with endpoints of overall survival, progression-free survival and response rates according to International Myeloma Working Group (IMWG) Uniform Response Criteria.

About NXC-201

NXC-201 (formerly HBI0101) is a BCMA-targeted investigational chimeric antigen receptor T (CAR-T) cell therapy that is being studied in a comprehensive clinical development program for the treatment of patients with relapsed or refractory multiple myeloma and amyloidosis. The design consists of a structurally differentiated CAR-T, with our proprietary BCMA-targeting CAR, which has demonstrated reduced toxicity in NEXICART-1, supporting investigating NXC-201 as an outpatient therapy.

About Multiple Myeloma
Multiple myeloma ("MM") is an incurable blood cancer of plasma cells that starts in the bone marrow and is characterized by an excessive proliferation of these cells. Despite initial remission, unfortunately, most patients are likely to relapse. There are 34,470 patients in the United States diagnosed with MM each year. Prognosis for patients who do not respond to or relapse after treatment with standard therapies, including protease inhibitors and immunomodulatory agents remains poor.

Hikma and Junshi Biosciences sign exclusive licensing agreement for cancer treatment drug toripalimab for the Middle East and North Africa region

On December 26, 2022 Hikma Pharmaceuticals PLC (Hikma), the multinational pharmaceutical company, reported a new exclusive licensing and commercialization agreement with Junshi Biosciences, an innovation-driven biopharmaceutical company, for toripalimab in the Middle East and North Africa (MENA) (Press release, Hikma, DEC 26, 2022, View Source [SID1234625640]). Under the terms of the agreement, Hikma has an exclusive license to develop and commercialize toripalimab injection in all its MENA markets. In addition, Hikma has the right of first negotiation for the future commercialization of three under development drugs in MENA.

Toripalimab is an innovative anti-PD-1 monoclonal antibody approved for marketing in China for six indications to date. Over thirty toripalimab clinical studies covering more than fifteen indications have been conducted globally, including in China, the United States, Southeast Asia, and Europe. Ongoing or completed pivotal clinical studies evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin, among others.

"We believe Hikma is the ideal partner for us in the MENA region. As the third largest pharmaceutical company in MENA, with a history of more than 40 years, Hikma is well established and respected and offers deep-rooted expertise, with unparalleled local knowledge. The company has also demonstrated strong commercial capabilities, particularly in areas such as oncology and biotechnology," said Dr. Ning LI, CEO of Junshi Biosciences. "We anticipate that toripalimab could be the first marketed Chinese anti-PD-1 antibody in MENA. We look forward to working closely with Hikma to establish toripalimab’s position in the MENA markets in order to provide patients with high-quality innovative care."

Commenting on this landmark agreement, Mazen Darwazeh, Hikma’s Executive Vice Chairman and President of MENA, said: "Anti-PD-1s have changed the way cancer is treated over the past few years but, unfortunately, patient access to these treatments in the region has been sub-optimal. Toripalimab has a compelling clinical profile with impressive efficacy and safety data, and we are thrilled to be collaborating with Junshi Biosciences to equip doctors and patients in MENA with this innovative treatment." He added, "This agreement strengthens our biotech and oncology portfolio and enables us to increase patients’ access to PD-1s, an important milestone in delivering on our purpose of putting better health, within reach, every day."

As part of this collaboration, Hikma has acquired rights to commercialize any combination product that comprises any therapeutically active pharmaceutical agent co-formulated or co-packaged with toripalimab. Hikma has also acquired exclusive rights of first negotiation to three of Junshi Biosciences’ novel oncology molecules.

About Toripalimab

Toripalimab is an anti-PD-1 monoclonal antibody developed for its ability to block PD-1 interactions with its ligands, PD-L1 and PD-L2, and for enhanced receptor internalization (endocytosis function). Blocking PD-1 interactions with PD-L1 and PD-L2 promotes the immune system’s ability to attack and kill tumor cells.

More than thirty company-sponsored toripalimab clinical studies covering more than fifteen indications have been conducted globally by Junshi Biosciences, including in China, the United States, Southeast Asia, and European countries. Ongoing or completed pivotal clinical trials evaluating the safety and efficacy of toripalimab cover a broad range of tumor types including cancers of the lung, nasopharynx, esophagus, stomach, bladder, breast, liver, kidney and skin.

In China, toripalimab was the first domestic anti-PD-1 monoclonal antibody approved for marketing (approved in China as TUOYI). Currently, there are six approved indications for toripalimab in China:

unresectable or metastatic melanoma after failure of standard systemic therapy;
recurrent or metastatic nasopharyngeal carcinoma (NPC) after failure of at least two lines of prior systemic therapy;
locally advanced or metastatic urothelial carcinoma that failed platinum-containing chemotherapy or progressed within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy;
in combination with cisplatin and gemcitabine as the first-line treatment for patients with locally recurrent or metastatic NPC;
in combination with paclitaxel and cisplatin in first-line treatment of patients with unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC);
in combination with pemetrexed and platinum as the first-line treatment in EGFR mutation-negative and ALK mutation-negative, unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
The first three indications have been included in the National Reimbursement Drug List (NRDL) (2021 Edition). Toripalimab is the only anti-PD-1 monoclonal antibody included in the NRDL for treatment of melanoma and NPC.

In the United States, the Food and Drug Administration (FDA) is reviewing the Biologics License Application (BLA) resubmission for toripalimab in combination with gemcitabine and cisplatin as first-line treatment for patients with advanced recurrent or metastatic NPC and for toripalimab monotherapy for the second-line or later treatment of recurrent or metastatic NPC after platinum-containing chemotherapy. The FDA has granted Breakthrough Therapy designations for toripalimab in combination with chemotherapy for the first-line treatment of recurrent or metastatic NPC as well as for toripalimab monotherapy in the second or third-line treatment of recurrent or metastatic NPC. Additionally, the FDA has granted Fast Track designation for toripalimab for the treatment of mucosal melanoma and Orphan Drug designations for the treatment of esophageal cancer, NPC, mucosal melanoma, soft tissue sarcoma, and small cell lung cancer (SCLC).

In Europe, marketing authorization applications (MAA) were submitted to the European Medicines Agency (EMA) and the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) in November 2022 for: 1) toripalimab combined with cisplatin and gemcitabine for the first-line treatment of patients with locally recurrent or metastatic NPC and 2) toripalimab combined with paclitaxel and cisplatin for the first-line treatment of patients with unresectable locally advanced/recurrent or metastatic ESCC. In December 2022, the EMA accepted the MAA.

Cellectis secures a €40 million credit facility from the European Investment Bank to support its Research, Development and Innovation activities

On December 28, 2022 Cellectis (Euronext Growth: ALCLS – NASDAQ: CLLS) (the "Company"), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, reported that it has entered into a €40 million credit facility agreement with the European Investment Bank ("EIB") (the "Finance Contract") (Press release, Cellectis, DEC 28, 2022, View Source [SID1234625639]).

The Company plans to use the facility toward the development of its pipeline in the field of allogeneic CAR T-cell product candidates, UCART22, UCART20x22, UCART123 and UCARTCS1.

The €40 million facility is divided into three tranches: €20 million for the first tranche ("Tranche A"), €15 million for the second tranche ("Tranche B") and €5 million for the third tranche ("Tranche C"). The disbursement of each tranches, including the first disbursement of Tranche A, is subject to certain conditions which, as of the date of this press release, remain to be satisfied.

The disbursement of Tranche A is subject to, among other things:

the execution of a warrant agreement (see hereafter) to be entered into with the EIB, issue of the warrants relating to Tranche A; and
the completion of certain clinical development milestone by Cellectis’ licensee.
The disbursement of Tranche B is subject to, among other things,

the full drawdown of Tranche A,
the issue of the warrants relating to Tranche B,
cash injection for an aggregate amount of at least €20 million as from October 31, 2022,
receipt by the Company of an aggregate amount of upfront and milestones payments in the context of existing or new partnerships of at least €15 million,
at least two clinical trials are actively recruiting,
no more than one clinical trial is ongoing mandatory holds
The disbursement of Tranche C is subject to, among other things,

the full drawdown of Tranche B,
the issue of the warrants relating to Tranche C,
cash injection for an aggregate amount of at least €25 million as from October 31, 2022,
receipt by the Company of an aggregate amount of upfront and milestones payments in the context of existing or new partnerships of at least €25 million,
at least two clinical trials are actively recruiting out of which one in the context of a pivotal study or at least two clinical trials are actively recruiting in the context of expansion phase studies,
at least two clinical trials are not ongoing mandatory holds
The three tranches will be available within 36 months following the signature of the Finance Contract.

"This EIB financing, which is minimally dilutive for our shareholders, is excellent news for Cellectis and a recognition of the work accomplished by our teams. It will allow us to support the development of our UCART product candidates" said André Choulika, Ph.D., Chief Executive Officer of Cellectis.

The credit will carry a decreasing fixed payment-in-kind (PIK) interest rate per tranche, with 8% for Tranche A, 7% for Tranche B and 6% for Tranche C, and with a maturity of six years for each tranche. Such PIK interest shall be capitalized annually, payable at maturity and added to the outstanding principal amount of the credit and therefore bear interest.

Subject to certain terms and conditions, upon the occurrence of standard events of default (i.e. including payment default, misrepresentation, cross default), EIB may demand immediate repayment by the Company of all or part of the outstanding debt and/or cancel any undisbursed tranches.

The Finance Contract will be supplemented by a warrants agreement to be concluded to determine terms and conditions of the warrants to be issued to the benefit of the EIB on which the Company will communicate on due course.