- Interim data from an investigator-initiated study in first-line maintenance setting for advanced pancreatic cancer suggest that Rubraca provides disease control with no new safety signals in 19 evaluable platinum-sensitive patients with germline BRCA1, germline or somatic BRCA2, or germline PALB2 mutations
- Clovis is evaluating a potential clinical and regulatory path forward for Rubraca in pancreatic cancer
- Nonclinical studies of rucaparib and lucitanib in multiple solid tumor types and Rubraca Trials in Progress posters also presented at AACR 2019
Tuesday, April 2, 2019
Clovis: Interim Results of Rubraca® (rucaparib) Phase 2 in Pancreatic Cancer
BioRad: Innovative Lyme Disease Diagnostic Test with FDA Clearance
Bio-Rad Laboratories, Inc. (NYSE: BIO and BIOb), a global leader of life science research and clinical diagnostic products, today announced that it has received U.S. Food and Drug Administration (FDA) clearance for its BioPlex 2200 Lyme Total Assay, an innovative multiplex test method to aid in the diagnosis of Lyme disease.
Lyme disease is the most common tick-borne illness in the United States. Many signs and symptoms of the disease are similar to other conditions so diagnosis can be challenging; however, individuals immediately treated for the disease usually recover rapidly and completely. The BioPlex 2200 Lyme Total Assay can simultaneously detect multiple targets, providing laboratories valuable information in the early stages of Lyme disease so patients are able to receive treatment as quickly as possible.
“The addition of the BioPlex 2200 Lyme Total assay broadens our BioPlex 2200 System infectious disease menu, offering laboratories the ability to detect Lyme disease at an early stage and thus fulfilling an important medical need in the management of Lyme disease,” said John Hertia, Bio-Rad President, Clinical Diagnostics Group.
The release of the BioPlex 2200 Lyme Total assay is the latest offering in Bio-Rad’s infectious disease menu for the BioPlex 2200 System, an automated multiplex technology platform. The BioPlex 2200 System provides clinical laboratories the capability to rapidly process or “multiplex” multiple individual tests that are traditionally processed separately, conserving patient sample volume and simplifying workflow.
Vistagen Positive Pilot Data Position Neuroactive Nasal Spray for Phase 3
VistaGen Therapeutics (NASDAQ: VTGN), a clinical-stage biopharmaceutical company developing new generation medicines for depression, social anxiety disorder and other central nervous system (CNS) diseases and disorders with high unmet need, announced today additional results from a positive pilot Phase 3 study of PH94B, a potential first-in-class neuroactive nasal spray shown to be effective on an as-needed (PRN) basis for treatment of social anxiety disorder (SAD).
The new data were presented in a poster session at the 2019 Anxiety and Depression Association of America (ADAA) Annual Conference in Chicago.
In the 22-patient, four-week, randomized, double blind, placebo-controlled pilot Phase 3 crossover study, subjects receiving PH94B had a significantly greater decrease in average peak Subjective Units of Distress scores compared to placebo within one week of treatment.1 There was also a significantly greater decrease in Liebowitz Social Anxiety Scale (LSAS) avoidance scores for subjects who received PH94B first, before crossing over to placebo. Administered at microgram doses and consistent with results from prior Phase 2 studies, PH94B’s safety profile was excellent, with no serious adverse events. VistaGen is currently preparing for pivotal Phase 3 development of PH94B as a novel first-line PRN treatment for SAD, with Dr. Michael Liebowitz, developer of the LSAS, a widely-used primary outcome measure in SAD for both clinical research and for evaluation in clinical practice, acting as Principal Investigator for the study.
WellCare Expands Medicaid Programs to 3 Additional NY Counties
WellCare Health Plans, Inc. (NYSE: WCG), a leading provider of Medicaid, Medicare and Prescription Drug programs, announced today that the New York Department of Health has approved the expansion of WellCare of New York, Inc. into three additional counties. The approval adds Broome, Richmond, and Suffolk counties to the company’s Medicaid Managed Care, Child Health Plus and Essential Plan programs, effectively immediately.
The expansion complements WellCare’s existing 16-county coverage area in Nassau, Kings, Queens, Manhattan, Bronx, Erie , Niagara, Steuben, Schuyler, Albany, Schenectady, Rensselaer, Duchess, Orange, Ulster and Rockland for Medicaid, Child Health Plus and Essential Plan programs.
“We are excited to have the opportunity to serve more members in New York, in partnership with the State, the new communities we are entering, and our providers,” said John J. Burke, president of WellCare of New York. “During the past several months, our team has diligently worked to build partnerships with providers and stakeholders in these new counties, and we look forward to helping more communities achieve better, healthier lives.”
WellCare has partnered with the New York Department of Health since 2002 to provide quality care for children, families, seniors and the disabled through Medicaid programs.
As of Dec. 31, 2018, WellCare serves approximately 295,000 members in New York, including 155,000 Medicaid members, 89,000 Medicare Advantage plan members and 52,000 Medicare Prescription Drug Plan members.
CytomX First-In-Class Probody Drug Conjugate To Target Tumor Antigen
– PROCLAIM-CX-2009 Dose Escalation Study Demonstrates Anti-Tumor Activity in Multiple Tumor Types –
– Preclinical Studies Suggest Role of CD166 Expression Level in Anti-Cancer Activity and Potential for Combination of CX-2009 with Immunotherapy –
CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational antibody therapeutics based on its Probody™ therapeutic technology platform, today announced the presentation of clinical and preclinical data for CX-2009, a CD166 targeting Probody Drug Conjugate (PDC), at the 2019 American Association for Cancer Research (AACR) Annual Meeting in Atlanta, Georgia.
“Collectively, these data highlight the potential opportunity for CX-2009, a novel first-in-class CD166-targeting anti-cancer agent,” said Sean McCarthy, D. Phil., president, chief executive officer and chairman of CytomX. “In our first clinical dose escalation with CX-2009, we have seen clear evidence of tumor shrinkage in multiple cancers in heavily pretreated patients and an encouraging safety profile. The safety profile of CX-2009 is of particular note given the widespread expression of CD166 on normal tissues and suggests that CytomX masking technology can allow targeting of novel, broadly distributed antigens. Moreover, our preclinical and clinical research is revealing a relationship between target levels and anti-cancer activity, further validating CD166 as a potential new point of intervention in cancer treatment. In addition, our preclinical research into the combination of CX-2009 with a PD-1 Probody provides preliminary evidence for the potential of these two mechanisms to synergize with each other. Based on these integrated observations presented at AACR 2019, we are excited to advance CX-2009 to the next phase of development.”
Chembio: with Perseus Science, to Advance Point-of-Care Concussion Test
Chembio Diagnostics, Inc.(Nasdaq: CEMI), a leading point-of-care diagnostics company focused on infectious diseases, today announced that the company has entered into an agreement with Perseus Science Group LLC, to advance the development of a diagnostic test for mild traumatic brain injury (TBI), or concussion. This agreement builds on previous agreements between the two firms that resulted in the completion of technical feasibility to detect Perseus’ patented biomarker.
Under terms of this agreement, Chembio will receive funding from Perseus, subject to satisfying certain milestones, to advance the development of a quantitative point-of-care test for concussion, combining Chembio’s proprietary DPP platform with Perseus’ biomarker. The DPP platform provides results in approximately 15 minutes from a small drop of fingertip blood.
Current methods for diagnosing TBI include neurological examination, cognitive testing, and imaging tests such as CT scan, MRI, and PET scans. Concussion is the most prevalent form of TBI and often goes undiagnosed at the time of injury. Rapid diagnosis of concussion using a point-of-care test could lead to earlier intervention and reduced incidence of secondary injuries.
“Our goal is to be first-to-market with a point-of-care diagnostic test for concussion,” stated John Sperzel, Chembio’s Chief Executive Officer. “We believe a rapid diagnostic test, performed with a small drop of fingertip blood, will aid in early diagnosis, reduced costs and improved outcomes for patients.”
According to 2017 U.S. Centers for Disease Control and Prevention estimates, in 2013 there were 2.5 million TBI-related emergency room visits – approximately one-third by children – and TBI contributed to approximately 30% of all injury deaths, making TBI a major cause of death and disability in the United States.
Next Frontier of CAR-T Therapies: Off-the-Shelf Therapies
Just over a year and a half ago, the U.S. FDA approved the first two CAR-T cell therapies:Novartis’ Kymriah for acute lymphoblastic leukemia (ALL) and Gilead-owned Kite Pharmaceutical’s Yescarta for certain types of large B-cell lymphomas, a type of non-Hodgkin lymphoma.
Those are both autologous therapies, meaning they are patient-specific. The patient’s own T-cells (a subtype of white blood cell) are collected from their blood, preserved and shipped to a manufacturer, genetically engineered to recognize and attack the patient’s cancer cells by modifying the T-cell’s receptors (now called chimeric antigen receptor T-cells, or CAR-T cells), then reintroduced into the patient via infusion.
While this type of personalized therapy is revolutionizing cancer treatment and healthcare, it has some formidable limitations.
Limitations with current autologous CAR-T therapies
Because it’s patient-specific, each treatment can only be used for that one patient; if patient B received patient A’s treatment, then patient A’s CAR-T cells would attack all of patient B’s cells (not just their cancer cells), recognizing them as ‘foreign’.
This patient-specific nature also means labor-intensive work and increased treatment production time – usually taking 3 to 4 weeks to manufacture – while running against the ticking cancer clock. Although a few weeks doesn’t sound like that long when you consider the work that goes into creating a personalized therapy, it is longer than many non-personalized treatments, which are available to the patient almost immediately.
The labor-intensive work to personalize the T-cells also heavily drives up the treatments’ price tags – $475,000 for Kymriah and $373,000 for Yescarta.
To resolve these issues, research is now pushing towards the next generation of CAR-T therapies – allogenic, or “off-the-shelf” treatments that can be mass manufactured from a healthy donor’s cells and used for multiple patients.
Off-the-shelf CAR-T therapy research
Researchers at University of California, Los Angeles (UCLA) were able to turn pluripotent stem cells (which can be changed into almost any cell type) into T-cells through structures called artificial thymic organoids. These organoids (miniature, simplified versions of three-dimensional organs derived from stem cells) mimic the thymus, the organ where T-cells are made from blood stem cells in the body.
In their study published in Cell Stem Cell in January, they demonstrated that the three-dimensional environment of artificial thymic organoids allows for successful T-cell maturation. Importantly, they created mature T-cells from both kinds of pluripotent stem cells used in research: human embryonic stem cells (from donated preimplantation human embryos) and induced pluripotent stem cells, called iPSCs (which are reprogrammed from healthy adult donor tissue, such as skin or blood cells).
“What’s exciting is the fact that we start with pluripotent stem cells,” Gay Crooks, the study’s senior author and director of the Cancer and Stem Cell Biology Program at the UCLA Jonsson Comprehensive Cancer Center, said in a press release. “My hope for the future of this technique is that we can combine it with the use of gene editing tools to create ‘off-the-shelf’ T-cell therapies that are more readily available for patients.”
The researchers showed that they could create T-cells that can target and kill tumors in mice by genetically engineering the pluripotent stem cells to express a specific cancer-targeting T-cell receptor.
“Once we create genetically edited pluripotent stem cell lines that can produce tumor-specific T-cells in artificial thymic organoids, we can expand those stem cell lines indefinitely,” said the study’s co-first author and Crooks’ lab associate project scientist Amelie Montel-Hagen.
As promising as this technology is, there are still some kinks to work out. Artificial thymic organoid-created T-cells still express surface molecules that would not match every patient, causing the patient to reject the T-cells.
“Our next step will be to create T-cells that have the receptors to fight cancer but do not have the molecules that cause the rejection of the cells, which would be a major step toward the development of universal T-cell therapies,” said Christopher Seet, the study’s other co-first author and a clinical instructor in the division of hematology-oncology at UCLA.
Their artificial thymic organoid technology was licensed to Gilead’s Kite Pharma back in July 2016. In April 2017, they first published their technology in Nature Methods, demonstrating that artificial thymic organoids allowed for T-cell maturation from adult blood stem cells. Kite has not released any further updates on their use of the organoid technology.
Off-the-shelf CAR-T therapies in biopharma
Off-the-shelf therapy is also a hot topic in biotechs now, with multiple companies working towards the next breakthrough therapy, including UCLA/Kite’s artificial thymic organoid technology.
Cellectis is a pioneer in gene editing (using TALEN technology) and allogeneic CAR-T therapy, also called Universal CAR-T cells (UCARTs). They have a range of UCARTs under development. UCART123, which targets CD123+ leukemic cells in acute myeloid leukemia (AML), is being studied in two currently recruiting open-label Phase 1 trials: AML123 studying the therapy’s safety and efficacy in an estimated 156 AML patients, and ABC123 studying the therapy’s safety and activity in an estimated 72 patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). UCART22 is designed to treat both CD22+ B-cell acute lymphoblastic leukemia (B-ALL) and CD22+ B-cell non-Hodgkin lymphoma (NHL). Cellectis reported that UCART22 is in an open-label, dose-escalating Phase 1 trial to study its safety and activity in relapsed or refractory CD22+ B-ALL patients. UCARTCS1 is being developed to treat CS1-expressing hematologic malignancies, such as multiple myeloma (MM). UCARTCLL1 is in preclinical development for treating CLL1-expressing hematologic malignancies, such as AML.
Cellectis is also jointly developing allogeneic CAR-T therapies with Allogene Therapeutics, another allogeneic CAR-T-focused biotech. ALLO-501 targets CD19 and is being developed to treat relapsed or refractory NHL. The FDA granted investigational new drug (IND) status to ALLO-501 in January and a Phase 1 trial is expected to begin within the next few months. Two therapies are exclusively licensed to Allogene: ALLO-715, which targets B-cell maturation antigen (BCMA), for treating relapsed or refractory MM; and ALLO-819, which targets CD135 (also called FLT3), for treating relapsed or refractory AML.
Allogene, in collaboration with Cellectis and Pfizer, have three active open-label, single-arm Phase 1 trials for an off-the-shelf allogeneic CAR-T therapy called UCART19 in patients with relapsed or refractory CD19+ B-ALL: PALL, which is studying the therapy’s safety and feasibility in 18 pediatric patients; CALM, which is a dose-escalating study evaluating the therapy’s safety and tolerability in 40 adult patients; and a long-term safety and efficacy follow-up study in 200 patients with advanced lymphoid malignancies.
Allogene reported some proof-of-concept results at the American Society of Hematology (ASH) meeting back in Dec 2018. Data from the first 21 patients from both the PALL (n=7) and CALM (n=14) Phase 1 studies were pooled. Of the 17 patients who received UCART19, fludarabine/cyclophosphamide (a standard chemotherapy drug combination that causes lymphodepletion, or destruction of lymphocytes and T-cells), and an anti-CD52 monoclonal antibody, 14 patients (82 percent) achieved complete remission with significant UCART19 cell expansion. In stark contrast, the four patients who only received UCART19 and fludarabine/cyclophosphamide (no anti-CD52 antibody) saw no response and minimal UCART19 expansion. This highlights the apparent importance of an anti-CD52 antibody for the efficacy of allogeneic CAR-T therapies. The safety data also looked relatively promising: no cases of grade 3 or 4 neurotoxicity, only 2 cases of grade 1 graft-versus-host disease (10 percent) and none any higher, 3 cases of grade 3 or 4 cytokine release syndrome that were “generally manageable” (14 percent), 5 cases of grade 3 or 4 viral infections (24 percent), and 6 cases of grade 4 prolonged cytopenia (29 percent).
Although this young allogeneic CAR-T technology is still being developed, sights are already set on what the manufacturing efficiency would be and how it would compare to autologous CAR-T therapy production. For example, Allogene states a potential to treat 100 patients per batch of allogeneic CAR-T cells.
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