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.

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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.

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]).

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"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.

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.

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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.

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]).

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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.

On December 28, 2022 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CFBI), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address inflammatory, cancer and liver diseases, reported an update on its clinical program for Namodenoson in the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer (Press release, Can-Fite BioPharma, DEC 28, 2022, View Source [SID1234625638]). A pivotal Phase III registration study is open for enrollment of the most advanced liver cancer patients. At two upcoming bio-partnering conferences, Can-Fite will be presenting the latest data comparing the response of liver cancer patients to those with HCC Child-Pugh B (CPB), the most advanced liver cancer. The Company will also share the latest findings on a CPB liver cancer patient who remains cancer-free 6 years after she began treatment with Namodenoson.

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Can-Fite’s prior Phase II study showed that median overall survival in the CPB7 patient population was 6.8 months for those treated with Namodenoson as compared to 4.3 months for those treated with placebo. The < 1-year survival in the whole patient population was 32% in the namodenoson treated group vs. 14% (p= 0.058) in the placebo treated patients whereas in the CPB7 population 44% survival was found in the namodenoson treated group vs. 18% in the placebo treated one (p=0.028). An article published in the peer-reviewed journal Cancers regarding Can-Fite’s Phase II study reported on the fact that CPB patients are generally excluded from clinical studies due to their poor prognosis and low expected response rate and that as of July 2020, clinicaltrials.gov listed 110 enrolling/active Phase II or III clinical studies in advanced HCC, all of which excluded CBP patients, except for only two studies in addition to Can-Fite’s.

"There is a dire need for a safe and effective treatment for patients with advanced liver disease, defined as CPB7 where Namodenoson has an advantage with its liver protective effect," stated Can-Fite CEO Dr. Pnina Fishman "Our Phase III pivotal Namodenoson study is open for enrollment of CPB7 patients who have tried but not benefitted from other treatments on the market. We are optimistic that Namodenoson can help these patients based on the overall survival benefit already demonstrated in our Phase II study. At the upcoming bio-partnering conferences, we will be sharing extensive data that compares how the overall liver cancer population is treated, while the CPB patient population has few options and there are very few drug developers that will even allow them into their studies."

Can-Fite has received agreement from both the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) on its Phase III pivotal liver cancer study which is now open for enrollment. Namodenoson has Orphan Drug status with both the FDA and EMA, as well as Fast Track Status with the FDA for the treatment of HCC. The double blind, placebo-controlled trial will enroll 450 patients diagnosed with HCC and underlying CPB7 through clinical sites worldwide. Patients will be randomized to oral treatment with either 25 mg Namodenoson or matching placebo given twice daily. The primary efficacy endpoint of the trial is overall survival. Other oncology trial efficacy outcomes, such as tumor radiographic response rates and median progression-free survival, as well as standard safety parameters, will be assessed.

An interim analysis will be conducted by an Independent Data Monitoring Committee (IDMC) after 50% of enrolled patients are treated. Namodenoson will be evaluated as a 2nd or 3rd line treatment for CPB7 patients in whom other approved therapies have not been or are no longer effective.

According to the American Cancer Society, liver cancer accounts for more than 700,000 deaths globally each year. HCC is commonly aggressive with poor survival rates. As new drugs that effectively and safely treat HCC are developed and approved, the market for HCC treatments is estimated by Delveinsight to reach $3.8 billion by 2027 for the G8 countries.

Conference Schedule:

Biotech Showcase: The Investor Conference for Innovators – San Francisco, Sari Fishman Ph.D. will participate.

Meeting Dates: January 9-11, 2023

Location: Hilton San Francisco Union Square

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BIO CEO & Investor Conference – New York, Motti Farbstein CFO will participate.

Meeting Dates: February 6-7, 2023

Location: New York Marriott Marquis

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About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.