Scholar Rock announced additional data on the mechanism of action of a highly specific inhibitor of TGFbeta1 activation in syngeneic mouse tumor models that emulate clinically-observed primary resistance to checkpoint blockade therapy. Detailed preclinical results are being presented at the American Association for Cancer Research, or AACR, annual meeting. The preclinical data demonstrate that treatment with SRK-181-mIgG1, a highly specific inhibitor of TGFbeta1 activation, in combination with an anti-PD1 immunotherapy, can drive tumor regression or control, resulting in significant survival benefit compared to anti-PD1 monotherapy, the company said. In addition, newly presented immune response data show that combination treatment leads to infiltration and expansion of CD8+ T cells and a reduction of immunosuppressive myeloid cells, suggesting TGFbeta1’s multiple contributions to primary resistance to CBT. “These new preclinical results reinforce our belief that a highly specific inhibitor of TGFbeta1 activation can enable the immune response to overcome a key mechanism of primary resistance to checkpoint blockade therapy, even in tumors that express other TGFbeta isoforms, and could meaningfully expand the number of patients who could benefit from checkpoint blockade therapies. With the recently announced nomination of SRK-181 as the first product candidate in our cancer immunotherapy program, we are eagerly working towards initiating a Phase 1 trial in patients with solid tumors in mid-2020,” said Nagesh Mahanthappa, President and CEO of Scholar Rock.
https://thefly.com/landingPageNews.php?id=2887591
Tuesday, April 2, 2019
Jounce Therapeutics reports new clinical data on vopratelimab
Jounce Therapeutics reported new clinical data on vopratelimab at the American Association for Cancer Research Annual Meeting. “The Jounce poster presentations show that patients in the ICONIC trial with emergence of ICOS hi CD4 T cells have improved progression free survival and overall survival compared to patients with ICOS lo CD4 T cells. Data related to important immune characteristics of ICOS hi CD4 T cells were also presented,” said the company. Three groups of Iconic relapsed refractory solid tumor patients were compared in the new analysis: 18 patients who have demonstrated ICOS hi CD4 T cells in the blood, 32 patients who have demonstrated ICOS lo CD4 T cells, and a group of patients enrolled in parts A through D which includes an additional 151 patients that were not tested for ICOS status due to lack of samples, according to Jounce. It added, “The emergence and persistence of the ICOS hi CD4 T cell biomarker in the peripheral blood is associated with improved PFS and OS: All benefit in the study, measured by tumor reductions, PFS and OS, was in the ICOS hi CD4 T cell group; PFS: median 6.2 months for patients with ICOS hi CD4 T cells vs 2 months for both patients with only ICOS lo CD4 T cells and All Patients; OS: median not yet reached for patients with ICOS hi CD4 T cells vs 9 months for patients with only ICOS lo CD4 T cells and 9.1 months for All Patients.” Richard Murray, CEO of Jounce Therapeutics, said, “We are encouraged by the improved PFS and OS data associated with the emergence of the ICOS hi CD4 T cell biomarker and are convinced that meaningful advancements in immuno-oncology will require the type of science-based translational understandings that the Jounce team and platform have enabled to advance vopratelimab thus far. We have established our translational technology base for the purpose of creating a preclinical and, more importantly, clinical scientific understanding of the mechanism of action of new immunotherapies and the characteristics of responding versus non-responding patients to focus the next steps of clinical development for vopratelimab and our pipeline.”
https://thefly.com/landingPageNews.php?id=2887593
https://thefly.com/landingPageNews.php?id=2887593
EDAP TMS SA Reports Q4 and Full Year 2018 Results
- Record fiscal year 2018 revenues of EUR39.2 million
- Q4 2018 HIFU net sales increased 79% year-over-year
- Profitable and cash flow positive during the fourth quarter of 2018
- Completed first U.S. sale of Focal One at the end of 2018
- Ended the year with a strong cash position of $22.3 million
EDAP TMS SA EDAP, +22.33% (“the Company”), the global leader in therapeutic ultrasound, announced today financial results for the fourth quarter and full year 2018 and provided a strategic and operational update.
Marc Oczachowski, EDAP’s Chief Executive Officer, said: “We are very pleased to report our fifth consecutive year of growth during 2018, achieving total revenue of EUR39.2 million. As announced, one of the major milestones during the year was FDA clearance of Focal One in June, and just six months later, we completed the first U.S. sale of Focal One to the John Wayne Cancer Institute. We followed that up with three additional U.S. Focal One sales in less than sixty days. Our HIFU sales and marketing development teams have also been very active outside of the U.S., with the opening of new markets and further expansion in existing countries such as Brazil.
“We experienced very strong momentum during the fourth quarter in the adoption of our HIFU technology in the U.S. and internationally. Our teams are fully focused on leveraging this positive trend to further develop our sales pipeline for 2019,” Mr. Oczachowski concluded.
Vaccinex up with AACR presentations
Ultra-thinly traded Vaccinex (VCNX +26%) is up on over 50% higher volume, albeit on turnover of only ~13K shares, on the heels of thee presentations at AACR related to its anti-SEMA4D technology.
The company states that the details of each of the three are on its website, but only the titles appear.
FDA to hold hearing on potential regulatory paths for cannabis products
The FDA issued a statement from outgoing Commissioner Scott Gottlieb on new steps to advance the agency’s continued evaluation of potential regulatory pathways for cannabis-containing and cannabis-derived products, in which he stated in part: “In recent years, we’ve seen a growing interest in the development of therapies and other FDA-regulated consumer products derived from cannabis and its components, including cannabidiol, or CBD…We also recognize that stakeholders are looking to the FDA for clarity on how our authorities apply to such products, what pathways are available to market such products lawfully under these authorities, and how the FDA is carrying out its responsibility to protect public health and safety with respect to such products.” The FDA is announcing a number of new steps and actions to advance its consideration of a framework for the lawful marketing of appropriate cannabis and cannabis-derived products under its existing authorities, Gottlieb said. These new steps include: A public hearing on May 31, as well as a broader opportunity for written public comment, for stakeholders to share their experiences and challenges with these products, including information and views related to product safety; The formation of a high-level internal agency working group to explore potential pathways for dietary supplements and/or conventional foods containing CBD to be lawfully marketed; including a consideration of what statutory or regulatory changes might be needed and what the impact of such marketing would be on the public health; Updates to its webpage with answers to frequently asked questions on this topic to help members of the public understand how the FDA’s requirements apply to these products; and the issuance of multiple warning letters to companies marketing CBD products with “egregious and unfounded claims that are aimed at vulnerable populations.” Publicly traded companies in the cannabis space include Aphria (APHA), Aurora Cannabis (ACB), CV Sciences (CVSI), CannTrust Holdings (CNTTF), Canopy Growth (CGC), Cronos Group (CRON), General Cannabis (CANN), India Globalization Capital (IGC), MediPharm Labs (MLCPF) and Tilray (TLRY).
Piper Jaffray says Crispr Therapeutics remains a top pick for 2019
Piper Jaffray analyst Edward Tenthoff reiterated an Overweight rating and $75 price target on Crispr Therapeutics, and added that Crispr remains a top pick for 2019, after the company announced the expansion of its wholly-owned allogeneic CAR-T pipeline at the American Association for Cancer Reseach, or AACR. Tenthoff said he expects more preclinical CAR-T data at the American Society of Gene and Cell Therapy, or ASGCT, in April. The analyst believes the biggest driver for the company remains “first-in-man Phase I/II CTX001 data in Beta-thal and potentially Sickle Cell Disease” this year.
https://thefly.com/landingPageNews.php?id=2887545
https://thefly.com/landingPageNews.php?id=2887545
Probiotics, touted as good for the gut, may be trouble for the immune system
Probiotics are wildly popular. After all, the microbial cocktails are available over the counter and have been shown to be helpful in the treatment of gastrointestinal illnesses for some people.
But some scientists worry probiotics aren’t as innocuous as they seem — and might be affecting the way other medicines work in the body.
The latest cautionary note comes in the form of a preliminary study released Tuesday, in which researchers found that melanoma patients were 70 percent less likely to respond to cancer immunotherapy if they were also taking probiotic supplements. The study group was small — just 46 patients — but the findings support broader suggestions that probiotics might actually upset the balance of so-called “good” bacteria in the gut and interfere with the immune response.
The research was conducted by MD Anderson Cancer Center in Houston and the Parker Institute for Cancer Immunotherapy in San Francisco.
“We wanted to bring this to the forefront of people’s minds: That probiotics sold over the counter aren’t necessary,” said Dr. Jennifer Wargo, lead author of the study and an associate professor of surgical oncology at MD Anderson. “They may not help you, and might even harm you.”
But because probiotics — like vitamins and other such supplements — are only loosely regulated by the Food and Drug Administration, consumers are free to sprinkle these prepackaged bacterial spores in with their standard therapeutic regimens. And that could have serious implications for their medical outcomes.
“I strongly, strongly question why the general public takes probiotics when medical evidence to this routine is not really available,” said Eran Elinav, an immunology researcher at the Weizmann Institute of Science in Israel.
Probiotic mixes vary dramatically from pill to pill. Companies aren’t even required to maintain the same combination of bacterial strains from one batch to the next, meaning what people put in their bodies could vary widely. Some of these strains may hinder the efficacy of one medicine, while others may enhance it.
There are too many unknowns to render any given probiotic totally safe, said Dr. Pieter Cohen, an associate professor of medicine at Harvard Medical School and an internist at Cambridge Health Alliance, who wrote about the issue last year in JAMA Internal Medicine.
Probiotics do work for some people, and some conditions: They’re helpful in treating colitis, for instance, and other gastrointestinal illnesses, said Dr. Rishi Sharma, a gastroenterologist in Walnut Creek, Calif.
Cancer patients often take probiotics to help mitigate some of the side effects of treatment — particularly diarrhea that stems from chemotherapy. While oncologists tend to be loathe to suggest their patients take over-the-counter probiotics, many with cancer still do: The MD Anderson study found that 42 percent of the patients studied were also taking probiotic supplements.
“When you see a study like this, suggesting immunotherapy might not work that well — I’d just avoid taking the probiotic,” Sharma said. “Your whole goal is to treat the cancer. And when it comes to probiotics, there’s just a lot of really bad data out there.”
Immunotherapies generally work in about a quarter of patients with certain cancers, but it’s still unclear exactly why. The MD Anderson/Parker Institute study was designed to probe whether there was a correlation between diet, the gut microbiome, and patient response to immunotherapy.
Forty-six metastatic melanoma patients beginning treatment at MD Anderson were asked to take a survey on what they ate and drank, and what supplements they took. Before the start of the therapy, researchers also took fecal samples from each patient — profiling the bacterial makeup of their respective microbiomes. The study also found that higher fiber intake was correlated with more lush microbiomes — and stronger responses to immunotherapy.
The research was presented as an abstract at the American Association of Cancer Research meeting this week in Atlanta. It hasn’t yet been published in a peer-reviewed journal.
“This study shows you that a patient’s response to immunotherapy is highly modulated by the microbiome,” said Elinav.
Elinav said the findings “are in perfect agreement” with conclusions from his own research: He published a pair of studies in Cell in 2018, finding that probiotic supplements actually decreased the diversity of participants’ microbiomes after they’d taken a course of antibiotics. In fact, the guts of those who took probiotics took much longer than those who did not to fully recover.
The MD Anderson/Parker Institute findings are far from conclusive. Wargo said that she and her team have been expanding the patient cohort being studied; they are also working with Seres Therapeutics, a Cambridge, Mass.-based biotechnology company, on whether bespoke combinations of probiotics might actually improve immunotherapy responses. Still, not all researchers are convinced by the early conclusions.
The Parker Institute is now conducting such a trial in collaboration with MD Anderson and Seres Therapeutics. This randomized, placebo-controlled clinical study is evaluating whether a specially designed oral microbiome pill with specific types of bacteria could positively impact a patient’s response to checkpoint inhibitors.
“I think it’s a provocative finding,” said Dr. Adil Daud, a professor of medicine and director of melanoma clinical research at University of California, San Francisco. “But I still think it’s too early to really conclusively say that probiotics interfere with immunotherapy.”
The trial was too small, and too many variables could have influenced its outcome, he said. Microbiota vary too significantly from person to person, and immunotherapy responses might even vary depending on age, ethnicity, and gender, Daud said. The study was too small to possibly take all of these factors into consideration, he said.
Daud noted that he did have one melanoma patient that he treated with pembrolizumab — an anti-PD-L1 immunotherapy — who actually seemed to benefit from probiotic use. Upon stopping a drug that had proved effective, the patient’s tumor began to grow back. When Daud restarted the pembrolizumab, the patient chose to also take a probiotic from Whole Foods; with the addition of the supplement, the same drug had a lasting effect on keeping the cancer at bay.
“But this is an isolated, n=1 case — so I don’t know how much weight this carries,” Daud said.
Daud tells his patients that, rather than focusing on probiotics, they’d be better served to work on their diet — increasing fiber intake, for instance.
Cohen, the internist at Cambridge Health Alliance, said he “can’t make heads or tails” of the latest study — it’s too small and vague, in his view.
“My two cents would be, this study reminds us that there’s no question that probiotics have a powerful impact on the immune system,” Cohen said. “That, and we have almost no data to demonstrate that these live microorganisms actually improve health.”
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