BUSINESS INSIGHTS, PHARMA TECH
Innate Pharma | January 17, 2023
On January 16, 2023, Innate Pharma SA announced the publication of preclinical findings demonstrating the control of acute myeloid leukemia (AML) cells by a trifunctional NKp46-CD16a-NK cell engager (NKCE) targeting CD123 in the scientific journal Nature Biotechnology. Innate and Sanofi conducted the experiments, which were published in Nature Biotechnology on January 12, 2023.
This study demonstrates that CD64 expression on AML blasts imparts resistance to anti-CD123 antibody-dependent cell cytotoxicity (ADCC) and that redirecting NK cells against cancer targets by binding to CD16a and NKp46 circumvents this resistance. Moreover, through their binding to NKp46, CD123-NKCE primarily target NK cells and have substantial antitumor activity against primary AML blasts; they stimulate NK cell activation and cytokine secretion exclusively in AML cells' presence.
In vivo, its antitumor activity observed in a mouse tumor model surpasses that of the anti-CD123 antibody used as the comparator. Furthermore, in vitro in human peripheral blood mononuclear cells and in vivo in nonhuman primates, the efficacy of CD123-NKCE was associated with the induction of low pro-inflammatory cytokine release and the absence of toxicity.
These results support CD123-NKCE clinical development. IPH6101/SAR'579 (SAR443579), the first NKp46/CD16-based CD123-targeted ANKETTM NK cell engager, is currently being evaluated in a Phase 1/2 clinical trial by Sanofi in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-ALL), or high-risk myelodysplastic syndrome (HR-MDS).
About Innate Pharma
Headquartered in Marseille (France), Innate Pharma SA is a global, clinical-stage oncology-focused biotech firm dedicated to enhancing patient treatment and clinical outcomes using therapeutic antibodies that employ the immune system to combat cancer. Its extensive antibody pipeline has numerous potentially first-in-class clinical and preclinical candidates for cancers with a high unmet medical need. In addition, Innate has been a pioneer in the study of natural killer cell (NK cell) biology and developed its expertise in tumor antigens, tumor microenvironment, and antibody engineering. This innovative strategy has resulted in a varied proprietary portfolio and substantial alliances with biopharmaceutical industry leaders, including Sanofi, Bristol-Myers Squibb, Novo Nordisk A/S, and a multi-product collaboration with AstraZeneca.
BUSINESS INSIGHTS, PHARMACY MARKET
RespireRX Pharmaceuticals Inc. | December 06, 2022
RespireRx Pharmaceuticals Inc. a leader in the discovery and development of innovative and revolutionary treatments to combat diseases caused by disruption of neuronal signaling, is pleased to announce that RespireRx has been accepted into the NIH HEAL Initiative® NINDS Preclinical Screening Platform for Pain program.
The Company’s lead GABAkine, KRM-II-81, has been shown to be effective in relieving acute, chronic, and neuropathic pain in a number of models without tolerance development or sedation.
The Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, is an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis. Launched in April 2018, the initiative is focused on improving prevention and treatment strategies for opioid misuse and addiction, and enhancing pain management.
The PSPP program, part of the NIH HEAL Initiative, evaluates non-opioid assets in a battery of established preclinical models. The PSPP program accepts small molecules, biologics, devices, or natural products for evaluation, from researchers in academia and industry worldwide.
The RespireRx team is led by Dr. Arnold Lippa, RespireRx Executive Chairman and Chief Scientific Officer and Drs. James M. Cook, Jeffrey M. Witkin and Rok Cerne, all of whom are RespireRx Research Fellows in addition to their academic affiliations at University of Wisconsin-Milwaukee, Ascension St. Vincent and Indiana University/Purdue University, respectively. The team has extensive expertise in drug discovery and development including the development of novel analgesic drugs and an extensive publication record with a combined total of over 1,000 scientific publications. The team has already profiled KRM-II-81 activity in a broad range of preclinical studies where it has displayed a high degree of analgesic activity and is excited at the prospect of advancing the Companay’s lead GABAkine toward clinical development. In cellular studies, KRM-II-81 preferentially bound to specific subtypes of GABAA receptors and boosted the ability of GABA to inhibit pain sensory neurons in the spinal dorsal root ganglia. In intact animal models of acute and chronic pain, the analgesic efficacy of KRM-II-81 was comparable to or greater than commonly used analgesics. At the same time, KRM-II-81 did not display side effects such as sedation and motor impairment, but even more importantly, it did not produce tolerance, dependence, respiratory depression, or behavioral changes indicative of abuse liability, which are produced by opioid narcotics and are at the heart of the opioid epidemic.
Unrelated to the NINDS project, KRM-II-81 has also shown promising results in multiple animal models of treatment resistant epilepsy and in human translational studies by reducing epileptiform electrical signaling in brain tissue removed from treatment resistant epileptic patients undergoing surgery.
Dr. Cerne commented “We believe that the expansion of our understanding of GABAA receptor structure and function has created a new surge in the discovery and development of GABAkines that target such receptors in a unique manner. This opens the promise of improved medicines for pain, epilepsy and other disorders caused by disruption of neuronal signaling.”
“We are very excited about developing KRM-II-81 and expanding the IND enabling studies so as to begin human studies. Pending clinical validation, we believe that KRM-II-81 has the potential to represent a breakthrough treatment for pain, epilepsy, and other neuropsychiatric disorders.”
About RespireRx Pharmaceuticals Inc.
RespireRx Pharmaceuticals Inc. is a leader in the discovery and development of medicines for the treatment of psychiatric and neurological disorders, with a focus on treatments that address conditions affecting millions of people, but for which there are few or poor treatment options, including attention deficit hyperactivity disorder epilepsy, pain, recovery from spinal cord injury ertain neurological orphan diseases and obstructive sleep apnea. RespireRx is developing a pipeline of new and re-purposed drug products based on our broad patent portfolios for two drug platforms: (i) pharmaceutical cannabinoids, which include dronabinol, a synthetic form of ∆9-tetrahydrocannabinol that acts upon the nervous system’s endogenous cannabinoid receptors and (ii) neuromodulators, which include AMPAkines and GABAkines, proprietary chemical entities that positively modulate AMPA-type glutamate receptors and GABAA receptors, respectively.
The Company holds exclusive licenses and owns patents and patent applications or rights thereto for certain families of chemical compounds that claim the chemical structures and their uses in the treatment of a variety of disorders, as well as claims for novel uses of known drugs.
GABAkines. Under a License Agreement with the University of Wisconsin-Milwaukee Research Foundation, Inc. and on behalf of its EndeavourRx business unit, RespireRx has licensed rights to certain selectively acting GABAkines because of their ability to selectively amplify inhibitory neurotransmission at a highly specific, subset of GABAA receptors, thus producing a unique efficacy profile with reduced side effects. Preclinical studies have documented their efficacy in a broad array of animal models of interrelated neurological and psychiatric disorders including epilepsy, pain, anxiety, and depression in the absence of or with greatly reduced propensity to produce sedation, motor-impairment, tolerance, dependence and abuse. The Company currently is focusing on developing KRM-II-81 for the treatment of epilepsy and pain.
BUSINESS INSIGHTS, PHARMA TECH
ADC Therapeutics | January 03, 2023
Sobi® and ADC Therapeutics SA informed that Zynlonta® (loncastuximab tesirine) has recently received conditional marketing authorization from the European Commission (EC) for the treatment of diffuse large B-cell lymphoma ((DLBCL) that has relapsed or become resistant. The approval comes after the European Medicines Agency's Committee for Medicinal Products for Human Use issued a favorable opinion in September.
Sobi has said that it wants to give Zynlonta, a new treatment for diffuse large B-cell lymphoma, to people in the European Union who have this debilitating blood cancer.
The approval was granted based on the findings from LOTIS-2, which was a large (n=145), phase 2 multinational, single-arm clinical study of Zynlonta for treating adult patients who had relapsed or refractory DLBCL following two or more prior lines of systemic therapy. Zynlonta was granted accelerated approval by the United States Food and Drug Administration in April 2021. This approval made it the first CD19-targeted antibody-drug conjugate to be used as a single-agent treatment for adult patients who had relapsed or been resistant to two or more lines of systemic therapy for their DLBCL.
Sobi announced an exclusive license agreement with ADC Therapeutics to develop and commercialize Zynlonta in Europe and other international markets. The license aims to boost Sobi's presence in hematology, one of its two main disease areas. Besides, Zynlonta will be sold with other Sobi hematology drugs.
ADC Therapeutics added that this approval expands Zynlonta's global reach. Zynlonta will fill a critical unmet need for DLBCL patients in Europe. The EU decision applies to Iceland, Norway, and Liechtenstein.
According to the terms of the license agreement and as previously communicated, Sobi will pay ADC Therapeutics USD 50 million as a result of the EU's approval of DLBCL. Sobi's clinical development and product supply are handled by ADC Therapeutics.
About ADC Therapeutics
ADC Therapeutics next-generation, targeted antibody-drug conjugates help cancer patients. With a deep understanding of oncology and an ADC platform that the FDA's approval of Zynlonta has proven, the company is working to meet unmet medical needs and improve outcomes for people with hard-to-treat hematological cancers and solid tumors. ADC Therapeutics' highly skilled global team is committed to fighting cancer with science, bringing targeted therapies and hope to patients and their families.