Cellectis: FDA Clears IND for 1st Allogeneic CAR-T for Multiple Myeloma

Cellectis, a biopharmaceutical company focused on developing immunotherapies based on gene-edited CAR T-cells (UCART), announced today that the U.S. Food and Drug Administration (FDA) has approved the Company’s Investigational New Drug (IND) application to initiate a Phase 1 clinical trial for UCARTCS1, in patients with multiple myeloma (MM). The IND for UCARTCS1 was filed on December 28, 2018 and approved by the FDA within a month, on January 25, 2019. Cellectis is the sponsor of the UCARTCS1 clinical study (MUNDI-01) and successfully ensured the manufacturing and release of UCARTCS1 GMP batches, as well as an IRB approval.

UCARTCS1 is based on a tailored manufacturing process developed by Cellectis, which removes both the CS1 antigen and TCR from the T-cell surface using TALEN^® gene editing technology, before adding the CS1 CAR construct. This approach has both clinical and operational benefits: the UCART is designed to have a lymphodepleting effect, and the CAR T-cell cross reaction is suppressed, allowing for successful manufacturing.

UCARTCS1 is the first allogeneic CAR-T therapy for MM to enter clinical development. This milestone reinforces Cellectis’ leadership in the space, as it represents the fourth TALEN^® gene-edited allogeneic CAR-T product candidate developed by Cellectis to be approved for clinical trials following UCART19¹ for ALL patients, UCART123 for AML patients and UCART22 for B-ALL patients. The Phase 1 of the MUNDI-01 study is designed to assess the safety and tolerability at increasing dose levels of UCARTCS1 in patients living with MM.

“The last quarters have been very productive for Cellectis’ UCARTCS1 product candidate. We successfully manufactured and released GMP batches of UCARTCS1, filed an IND and secured approval from the FDA to start the MUNDI-01 Phase 1 clinical study,” said Dr. André Choulika, Chairman and CEO of Cellectis. “This is the 4^th time in 4 years that Cellectis demonstrates excellence with an allogeneic product candidate. It further demonstrates the strength of our innovation, our manufacturing process and our execution, as we are eager to bring the first allogeneic multiple myeloma CAR T-cell treatment to patients.”

https://www.marketscreener.com/CELLECTIS-42457/news/Cellectis-FDA-Clears-the-IND-for-UCARTCS1-the-First-Allogeneic-CAR-T-to-Treat-Multiple-Myeloma-Pa-28341063/

Purdue’s Sackler family fights ‘inflammatory’ Massachusetts opioid case

Members of the Sackler family behind OxyContin maker Purdue Pharma LP have asked a judge to toss a lawsuit by Massachusetts’ attorney general claiming they helped fuel the U.S. opioid epidemic, arguing it contains “misleading and inflammatory allegations.”

The wealthy family in a motion on Monday argued that Massachusetts Attorney General Maura Healey, who brought the suit, had mischaracterized internal records to create the “false impression” they personally directed privately-held Purdue’s marketing of painkillers.

Her lawsuit, filed in June in Suffolk County Superior Court and revised earlier this year to include new allegations, was the first by a state to try to hold Sackler family members personally responsible for contributing to the opioid epidemic.

The case is among roughly 2,000 lawsuits filed by state and local governments seeking to hold Purdue and other pharmaceutical companies responsible for the U.S. opioid crisis.

Opioids were involved in a record 47,600 overdose deaths in 2017 in the United States, according to the U.S. Centers for Disease Control and Prevention.

Healey’s complaint cites records to argue that family members, including Purdue’s former President Richard Sackler, personally directed deceptive opioid marketing while making $4.2 billion from Purdue from 2008 to 2016.

They did so even after Purdue and three executives in 2007 pleaded guilty to federal charges related to the misbranding of OxyContin and agreed to pay a total of $634.5 million in penalties, the lawsuit said.

But in their motion, the Sacklers said nothing in the complaint supports allegations they personally took part in efforts to mislead doctors and the public about the benefits and addictive risks of opioids.

They said their role was limited to that of typical corporate board members who participated in “routine” votes to ratify the management’s staffing and budget proposals.

“Not a single document shows an individual director engaging in any unlawful conduct regarding the sale of prescription opioids or ordering anyone else to do so,” the Sacklers’ lawyers wrote.

Healey’s office had no comment.

At least 35 states have cases pending against Purdue. A handful have also named Sackler family members as defendants, including Richard Sackler, Theresa Sackler and Mortimer D.A. Sackler.

Last week, Purdue reached its first settlement in the recent wave of lawsuits, agreeing with the Sacklers to a $270 million deal with Oklahoma’s attorney general. The Sacklers were not named as defendants in Oklahoma’s lawsuit.

Purdue had been exploring filing for bankruptcy before the accord’s announcement, Reuters reported in early March.

https://www.marketscreener.com/news/Purdue-s-Sackler-family-fights-inflammatory-Massachusetts-opioid-case–28340701/?countview=0

Gritstone presents data on indentifying MHC class 2 antigens at AACR

Gritstone Oncology announced the presentation of data demonstrating its ability to identify major histocompatibility complex, or MHC, class 2 antigens at the American Association for Cancer Research, or AACR. In an oral presentation, it was shown that Gritstone Edge improved the positive predictive value for human leukocyte antigen class II, or HLA-DR, peptide presentation over standard methods by approximately 20-fold. Edge is an artificial intelligence platform that identifies tumor-specific neoantigens, or TSNA, for the development of antigen-directed immunotherapies that may drive highly specific tumor cell destruction by T cells. TSNA can be presented by either MHC class I, which are recognized by CD8 T cells, or MHC class II, which are recognized by CD4 T cells. The public tools available to predict tumor-specific antigens presented by MHC class I are more advanced; historically, the characterization of MHC class II presented antigens has been challenging for the field due to greater variability in their binding properties. The MHC class II dataset for the AACR analyses was derived from 73 human tumor and cell-line samples, including non-small cell lung cancer, lymphoma and ovarian cancer. The data sat is comprised over forty-five thousand tumor-presented peptides. Building on the progress with class I Edge, Gritstone’s class II model overcame a challenge with HLA class II prediction, which is the longer and more variable presented peptide lengths. Gritstone addressed this challenge with the new comprehensive training dataset and an innovative neural network architecture, leading to an approximately 20-fold increase in performance when using Edge versus standard methods. This dataset complements the previously reported Edge data demonstrating that it is approximately nine-fold better than publicly available tools at predicting tumor-specific antigens presented by MHC class I.
https://thefly.com/landingPageNews.php?id=2887651

Akebia selloff on ‘stale’ safety concern an overreaction, says Raymond James

Raymond James analyst Reni Benjamin attributes the selloff today in shares of Therapeutics to “stale” vadadustat safety concerns. After speaking with management the analyst views the selloff as an overreaction.
https://thefly.com/landingPageNews.php?id=2887649

Nektar presents data on its immuno-oncology pipeline candidates

Nektar Therapeutics presented preclinical data on its immuno-oncology pipeline candidates, bempegaldesleukin,NKTR-214 or bempeg, a CD122-preferential IL-2 pathway agonist, and NKTR-255, an IL-15 receptor agonist, at the American Association for Cancer Research Annual Meeting 2019. The meeting is being held on March 29 to April 3, 2019 at the Georgia World Congress Center in Atlanta. “We’re excited to showcase our promising immuno-oncology pipeline, which is strategically developed to target multiple points in the cancer immunity cycle to amplify the body’s ability to fight tumor cells,” said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar. “The preclinical studies presented at AACR 2019, by both Nektar scientists and our collaborators highlight the promise of targeting the IL-2 and IL-15 pathways to activate the immune system to induce durable anti-tumor responses in combination with complementary mechanisms such as personalized T cell vaccines and tumor-directed antibody therapies. We plan to explore these combinations further and look forward to advancing them into the clinic.”

https://thefly.com/landingPageNews.php?id=2887630

Doctors Unclear on Legal Obligations in Caring for Patients With Disability

Practicing physicians might not understand their legal responsibilities when caring for people with disability, which may contribute to inequalities in their care, according to a study published online April 1 in Health Affairs.

Nicole D. Agaronnik, from Massachusetts General Hospital in Boston, and colleagues interviewed 20 practicing physicians across five specialties to examine the knowledge of their obligations to accommodate patients with disability under federal civil rights law.

The researchers found that in three potentially problematic areas, interviewees reported having had little formal training about their obligations and demonstrated superficial or incorrect understanding of their obligations; these areas were deciding which accommodations their practices should implement, refusing patients with disability, and holding patients accountable for accommodation costs.

“Our findings suggest that physicians have little formal training in legal requirements to provide equitable care to people with disability. Thus, perhaps not surprisingly, our results also suggest that practicing physicians might not fully understand their legal responsibilities when caring for people with disability,” the authors write. “Therefore, one critical future direction involves educating physicians on several levels — about disability disparities, their legal obligation to provide equitable care and reasonable accommodations, and approaches to accommodating disability.”

Abstract/Full Text (subscription or payment may be required)

https://www.physiciansbriefing.com/internal-medicine-21/doctor-news-206/doctors-unclear-on-legal-obligations-in-caring-for-patients-with-disability-744466.html

Reduction in Autism Diagnoses Observed With Revised Diagnostics Manual

Use of the Diagnostic and Statistical Manual 5 (DSM-5) criteria for autism spectrum disorder (ASD) seems to have reduced the number of ASD diagnoses, according to a review published online March 9 in the Journal of Autism and Developmental Disorders.

Kristine M. Kulage, M.P.H., from the Columbia University School of Nursing in New York City, and colleagues examined changes in the frequency of ASD diagnoses since the DSM-5 publication in a five-year follow-up systematic review and meta-analysis. Data were included for 33 studies.

The researchers found that use of DSM-5 criteria indicates reductions in the diagnosis of ASD (20.8 percent; P < 0.001), DSM-IV-TR autistic disorder (10.1 percent; P < 0.001), and Asperger syndrome (23.3 percent; P = 0.001); a nonsignificant decrease was seen in pervasive developmental disorder-not otherwise specified (46.1 percent; P = 0.52). Overall, 28.8 percent (P = 0.06) of individuals diagnosed with DSM-IV-TR but not DSM-5 ASD would qualify for social communication disorder. Compared with earlier reviews, the findings suggested smaller decreases in ASD diagnoses.

“Our findings provide further insight regarding how the DSM-5 is being used nationally and internationally to diagnose, or failing to diagnose, those with ASD,” Kulage said in a statement. “Future research is needed, as concerns remain for impaired individuals, who, because of the change in diagnostic criteria for ASD, may no longer qualify for treatment but still demonstrate a need for services.”

Abstract/Full Text (subscription or payment may be required)

https://www.physiciansbriefing.com/pediatrics-15/autism-news-51/reduction-in-autism-diagnoses-observed-with-dsm-5-744024.html