Stem Cell Clinic

Novel CAR T-Cell Therapy Shows Promise in Advanced Hodgkin Lymphoma – Curetoday.com

Unlike other CAR T-cell therapies, clinical success was not associated with significant complications from therapy, said Dr. Jonathan Serody. This means this treatment should be available to patients in a clinic setting and would not require patients to be hospitalized, which is critical in our current environment.

Results from the parallel phase 1 and phase 2 studies also demonstrated that the CAR T-cell therapy was safe and did not produce any serious or severe side effects.

Researchers from the UNC Lineberger Comprehensive Cancer Center and Baylor College of Medicine administered anti-CD30 CAR T cells to 41 patients with relapsed or refractory Hodgkin lymphoma. All patients underwent lymphodepletion with bendamustine alone, bendamustine and fludarabine, or cyclophosphamide and fludarabine prior to the anti-CD30 CAR T-cell therapy.

Measuring safety was the primary goal of the two parallel studies.

The overall response rate, or the percentage of partial or complete responses to therapy, among 37 evaluable patients was 62%. Thirty-four of the patients received fludarabine-based lymphodepletion 17 of which received it with bendamustine, and the other half received it with cyclophosphamide. Two of these patients were considered to be complete response at infusion and maintained the response, so they were not included in final analysis.

The overall response rate among the remaining patients was 72%, with 59% of patients achieving a complete response. After a median follow-up of 533 days, researchers identified the one-year progression free survival rate to be 36% and the one-year overall survival rate to be 94%.

This is particularly exciting because the majority of these patients had lymphomas that had not responded well to other powerful new therapies, said senior study author Dr. Barbara Savoldo, professor in the Department of Microbiology and Immunology at the UNC School of Medicine, in a press release. Patients within the study had received a median of seven previous lines of therapy that included checkpoint inhibitors and autologous or allogeneic stem cell therapies, therapies known to be powerful but also tend to come with a host of side effects.

However, treatment with the anti-CD30 CART cells demonstrated a favorable safety profile. Although 10 patients developed cytokine release syndrome, all cases were considered minor.

Patients who received fludarabine-containing lymphodepletion were the only participants in the study to have a response to the anti-CD30 CAR T-cell therapy.

Although CD30 CAR T (cells) showed modest activity in (Hodgkin lymphoma) when infused without lymphodepletion, robust clinical responses were achieved when these cells were infused in hosts lymphodepleted with fludarabine-containing regimens, the authors wrote.

The activity of this new therapy is quite remarkable and while we need to confirm these findings in a larger study, this treatment potentially offers a new approach for patients who currently have very limited options to treat their cancer, said Dr. Jonathan Serody, director of the bone marrow transplant and cellular therapy program at UNC Lineberger Comprehensive Cancer Center, in the release. Additionally, unlike other CAR T-cell therapies, clinical success was not associated with significant complications from therapy. This means this treatment should be available to patients in a clinic setting and would not require patients to be hospitalized, which is critical in our current environment.

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Novel CAR T-Cell Therapy Shows Promise in Advanced Hodgkin Lymphoma - Curetoday.com

Sapience Therapeutics Announces First Patient Dosed with ST101 in Phase 1/2 Study in Patients with Advanced Unresectable and Metastatic Solid Tumors |…

Details Category: Proteins and Peptides Published on Thursday, 13 August 2020 10:22 Hits: 282

HARRISON, NY, USA I August 12, 2020 I Sapience Therapeutics, Inc., a biotechnology company focused on the discovery and development of peptide therapeutics to address difficult-to-treat oncology indications, today announced dose administration for the first patient in a Phase 1/2, open-label, dose escalation and expansion study of single agent ST101, a peptide therapy being evaluated for the treatment of adults with unresectable and metastatic solid tumors who are not eligible for other therapies or have progressed on prior therapies.

"The initiation of this study represents a significant milestone for Sapience, as it marks the first program from our portfolio of peptide therapies to enter the clinic," said Alice Bexon, M.D., Chief Medical Officer of Sapience Therapeutics. "The ST101 program highlights Sapience's therapeutic approach of using peptides to target intracellular protein-protein interactions, which are often referred to as 'Undruggable Targets'. Through this study, we anticipate generating a wealth of clinical data to guide our future development plans for this first-in-class antagonist of C/EBP."

Nehal Lakhani, M.D., Ph.D., Director of Clinical Research at START Midwest (South Texas Accelerated Research), and a clinical investigator on the study added, "We are eager to explore the profile of ST101 and to investigate the role of C/EBP inhibition for the treatment of advanced solid tumors. We are always looking for opportunities to accelerate the development of new treatments to improve patients' lives and give them hope against cancer, and ST101 holds that potential."

The Phase 1/2 trial will enroll patients at several leading clinical centers in the US and UK. The trial will start with a dose escalation phase to assess the safety and tolerability of ST101, followed by an expansion phase to evaluate preliminary efficacy in patients with glioblastoma, locally advanced/metastatic breast cancer, castration-resistant prostate cancer and melanoma. Please refer to http://www.clinicaltrials.gov for additional information (NCT 04478279).

About ST101

ST101 is a peptide antagonist of the transcription factor C/EBP, which is typically expressed and active in stem cells or early progenitor cells but not in most mature or differentiated cells. Certain cancers activate C/EBP, which results in the expression of genes with roles in cell proliferation, differentiation, and the cell cycle. Disruption of this transcription factor with ST101 results in targeted killing of cancer cells, as normal cells do not rely on C/EBP driven transcription for survival.

About Sapience Therapeutics

Sapience Therapeutics, Inc., is a privately held, clinical stage biotechnology company focused on discovering and developing peptide-based therapeutics for major unmet medical needs, particularly high mortality cancers. With platform-based discovery of peptide therapeutics that disrupt protein-protein interactions, Sapience's molecules hold potential to target intracellular interactions that are traditionally considered "undruggable targets". Its lead compound, ST101, is a first-in-class molecule with potential applications in various solid tumors and hematologic malignancies. For more information on Sapience Therapeutics, please visit http://www.sapiencetherapeutics.com.

SOURCE: Sapience Therapeutics

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Sapience Therapeutics Announces First Patient Dosed with ST101 in Phase 1/2 Study in Patients with Advanced Unresectable and Metastatic Solid Tumors |...

Novo backs ‘breakthrough’ antifungal player’s $60M round with a focus on rare mold infections – Endpoints News

The plight of antibiotics developers has been well documented: chronically underfunded research, daunting scientific challenges, and little commercial upside even for the ones that make it to the market. But in an adjacent corner of the antimicrobial space, an antifungal player is out to paint a very different picture.

F2G, a UK-Austria hybrid, has raised $60.8 million for its final push toward the clinic. Clearing the test could pave the way for its drug to be the first new antifungal agent in 20 years.

Thats how sparse the landscape has been, CEO Ian Nicholson told Endpoints News.

Its not for the lack of need, Nicholson noted. Much like in the antibacterial space, antifungal resistance is common occurring in 30% of patients taking the mainstay triazoles. Left untreated, the mortality rates for some of these rare mold infections targeted by F2G can be between 90% and 100%. Because fungi are eukaryotes just like humans, it has been difficult to discover new targets and corresponding new chemical entities.

The biotech began as a spinout of the University of Manchester, tapping into technologies that enabled them to manipulate and analyze fungal genes. F2G scientists eventually zeroed in on DHODH or dihydroorotate dehydrogenase, a key enzyme that helps fungi create the building blocks it needs to grow.

As it turned out, this blockade also kills the fungus. Out of this new class of antifungals dubbed orotomides, the lead candidate olorofim has been designated a breakthrough therapy (a first for antifungals, according to Nicholson), an orphan drug as well as a qualified infectious disease product. The ongoing open label Phase IIb study is testing it in a variety of rare mold infections, including invasive aspergillosis, scedosporiosis, lomentosporiosis, fusariosis, scopulariopsosis and coccidioidomycosis (valley fever).

For the upcoming Phase III, though, F2G plans to focus solely on invasive aspergillosis where a single study involving a couple hundred patients is expected to cement approval.

Valley fever is also a top priority in the US, where CMO John Rex, the former head of infection at AstraZeneca, leading a clinical team.

Compared to bacterial infections, fungal infections typically need to be treated for much longer, a matter of months rather than days. Theres no abundance of cheaply priced generics, and payers that F2G has talked to agreed that any new entrants should be priced relatively high.

Its a similar therapeutic area, but in many respects commercially it is much more like a rare disease drug than conventional anti-infective drug, CFO Ralf Schmid said.

Citing Gileads AmBisome as an example and an entrenched rival, Schmid pointed out the drug can cost $1,400 per day despite the availability of generics.

Just to set the context, added Naveed Siddiqi, a partner at Novo Ventures, the big drugs in the states are voriconazole and propiconazole, and they both at peak sold somewhere between $700 million and over $800 million.

Novo came on board for the first $60 million round back in 2016. Morningside Ventures, another existing investor, stepped up for the new funding alongside Brace Pharma Capital, Advent Life Sciences and new backer Cowen.

In addition to funding the clinical trial, the financing is also expected to scale up the current 20-person team in preparation for launch. Nicholson said the growth will be substantial but dont expect it to match the pharma rivals.

Because these infections occur in the context of transplants or cancer, when theyre immunosuppressed, a small company with a relatively limited salesforce and commercial organization can actually address this, Siddiqi said.

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Novo backs 'breakthrough' antifungal player's $60M round with a focus on rare mold infections - Endpoints News

CanSino reaps $748M windfall from Shanghai IPO as it warns Covid-19 vaccine won’t be a huge money maker – Endpoints News

CanSino began the year with a clear goal to secure a secondary listing on Shanghais STAR market. Then something more urgent came along: As a rising vaccine developer on a mission to bring global standard immunizations to China, it heeded the call to make a vaccine to protect against a virus that would paralyze the whole world.

Xuefeng Yu and his team managed to keep doing both.

More than a month after CanSinos Covid-19 vaccine candidate is authorized for military use in China, the Hong Kong-listed company has made a roaring debut in Shanghai. It fetched $748 million (RMB$5.2 billion) by floating 24.8 million shares, and soared 88% on its first trading day.

At RMB$209.71 apiece, its the second most expensive IPO ever on the nascent tech board, according to the South China Morning Post.

In opening the STAR market last year, Shanghais stock exchange followed its Hong Kong counterparts footsteps. By lowering the listing requirements to accommodate pre-revenue tech and biotech companies, both bourses are looking to lure domestic upstarts back from Nasdaq.

Its not uncommon for STAR stocks to jump dramatically or even double upon their debuts. In fact, CanSino closed at a lower price than expected.

The first-day gain turned out to be smaller than traders expected because of worries about frothy valuations on the overall A-share market, Ivan Li, a money manager at Shanghai-based Loyal Wealth Management, told SCMP. But investors still have confidence in the stock and its vaccines in the pipeline.

Covid-19 has delayed clinical plans for its earlier-stage vaccines, CanSino reported in its prospectus, which are candidates designed to protect against pneumococcal diseases as well as diphtheria, tetanus and pertussis.

Meanwhile, logistical troubles are still stalling the plan to test the coronavirus vaccine, Ad5-nCoV, in Canada. With political tension and speculation running high, CanSino has turned to Saudi Arabia to kick off its first Phase III test like all the other Chinese vaccine makers, its opting to do late-stage studies in places where infections are still widespread.

Even if the Phase III results are positive, though, dont expect it to be a money maker. CanSino noted that the Chinese government might be taking control of pricing and supply as well as exports, leading to a lower profit margin than other products.

An Ebola vaccine developed with a scientist from Chinas army whos also a collaborator on the Covid-19 program remains the only approved product in CanSinos portfolio. Two meningococcal vaccines are now under regulatory review.

The company wrote that its building a sales and marketing team, with the goal being to expand from the current 20-plus to 100 by the end of 2020.

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CanSino reaps $748M windfall from Shanghai IPO as it warns Covid-19 vaccine won't be a huge money maker - Endpoints News

Roche pulls a tumor micro-environment drug out of the freezer, hands it to a UK upstart – Endpoints News

Two years after pulling it from clinical development, Roche has handed control of a solid tumor cancer drug to a tiny Oxford University spinout.

For an undisclosed fee, Celleron Therapeutics acquired the drug, an anti-CSF1R antibody thats designed to modulate the tumor micro-environment an increasingly popular approach among cancer drug developers. Celleron says it will now put the drug into trials for patients with tenosynovial giant cell tumors, a rare disease where series of benign tumors begin to grow around the joints and tendons. Its caused by cells over-producing CSF1R.

The deal appears to be a straight biotech-repurposing-off-the-Pharma-shelf deal. Although Roche launched 4 different trials for the drug one of which is still technically on-going the Swiss pharma retired the drug as part of a broad pipeline sweep back in October of 2018. It was a business decision, the company wrote on one withdrawn studys page on clinicaltrials.gov, stipulating there were no safety or efficacy concerns.

In fact, the antibody had looked promising in the only efficacy results that ever surfaced. In a Phase I study published in The Lancet Oncology, 24 out of 28 patients responded to the drug, and two of them had a complete response.

Celleron will now have a chance to test whether those results can bear out in larger trials. The company says its built a proprietary platform around epigenetic control and immune modulation, but most of their clinical efforts so far have focused on an in-licensed drug from AstraZeneca that inhibits histone deacetylase, a class of enzymes that change one of the types of epigenetic markers on DNA. Theyve put it into Phase I and Phase II trials in the UK and in China in different combinations and different cancers, including T-cell lymphomas and HCC.

Still, Celleron has its own assets, including a series of preclinical assets that target histones. They also have CXD201, a molecule that inhibits topoisomerase, one of the enzymes that winds and unwinds DNA. And they say they use biomarker data to match the best drugs to the best patients.

The company has never announced how much capital theyve raised, but they said in 2017 they raised funding from a South Korean consortium.

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Roche pulls a tumor micro-environment drug out of the freezer, hands it to a UK upstart - Endpoints News