On June 2, 2022 MaaT Pharma (EURONEXT: MAAT – the "Company"), a French clinical-stage biotech and a pioneer in the development of Microbiome Ecosystem TherapiesTM (MET) dedicated to improving survival outcomes for patients with cancer, reported completion of its Phase 1b CIMON trial evaluating the safety and tolerability of MaaT033, the Company’s high-richness, high-diversity MET for oral administration, in patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HRMS) having received intensive chemotherapy (Press release, MaaT Pharma, JUN 2, 2022, View Source [SID1234615420]). In this study, performed in an immuno-compromised patient population, MaaT033 presented a good safety and tolerability profile, evaluated as the primary endpoint. The topline results also show rapid and persistent engraftment of MaaT033 in the patients’ gut. The study data support the Company’s preparation to initiate a Phase 2/3 trial later this year to evaluate MaaT033’s ability to improve survival and prevent complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with blood cancers. Every year, approximately 22,000 patients require allo-HSCT in the seven major markets. MaaT033’s oral formulation is designed to support long-term, ambulatory use, opening up new potential development opportunities for the Company. Today’s announcement confirms previously-announced promising interim results of the trial, which allowed early completion of the study.

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"Parallel to the clinical successes of our lead candidate MaaT013, we developed MaaT033 as our first oral formulation, and the strength of the engraftment we have seen in these cohorts exceeds our expectations. Together with a good safety profile, this solid evidence for our first oral candiate is a crucial milestone for MaaT Pharma," commented Hervé Affagard, CEO and co-founder of MaaT Pharma. "Allo-HSCT is a curative treatment of liquid tumors, that is unfortunately negatively impacted by two primary complications, graft-versus-host disease and severe infections, which hinder overall survival. We view the prevention of these adverse effects as the key to a better prognosis for these patients."

MaaT033 is designed to restore and maintain a healthy gut microbiome in patients with severe dysbiosis as a result of intensive chemotherapy and antibiotic treatment. Developed as an oral formulation in lyophilized capsules, its proprietary targeted-delivery design is conceived to optimize the product’s engraftment in the patient’s gut and its interaction with the immune system. Thanks to its high bacterial richness and ButycoreTM content, the product aims to reorient the gut microbial network towards immune homeostasis and restore the microbiome’s intestinal barrier function against infections.

"We know from previous studies that AML patients are highly dysbiotic as a result of intensive chemotherapy and antibiotic therapy. From the CIMON trial data, we can be confident that MaaT033 results in robust levels of engraftment in the gut of AML patients at the targeted dose," said Prof. Christian Recher, Professor of Hematology at the Toulouse University Hospital/IUCT-Oncopole (France) and Principal Investigator of the study. "This strong foundational data supports the launch of the next phase evaluating MaaT033 in preventing allo-HSCT complications in this patient population."

The CIMON Phase 1b trial (NCT04150393) was an open-label, dose-ranging study investigating the maximum tolerated dose of MaaT033 in patients with acute myeloid leukemia or high-risk myelodysplastic syndrome who have undergone intensive chemotherapy. The trial enrolled 21 patients in four dose escalation cohorts (up to three capsules a day for 14 days) across six sites in France. The trial allowed to select the recommended dose for MaaT033, which remains confidential at this stage. MaaT033 showed rapid and persistent engraftment with the detection of more than 60% of the MaaT033 microbial communities (OTUs) in the patient’s gut post-exposure at the selected dose. Substantial engraftment was maintained during the treatment period and for at least three weeks after the end of treatment (last measure). Good tolerability of the candidate was also observed in this immunocompromised population, with only four serious adverse events (SAE) considered as unrelated to the treatment and one possibly related SAE (an infectious diarrhea event with no detection of the causal pathogen in the administered MaaT033 and patient recovery within four days). This is in line with the expected AE profile with standard of care treatments in this fragile population.

MaaT Pharma has performed a Scientific Advice procedure with the European Medicine Agency and will move forward with preparations for a Phase 2/3 randomized, double-blind, placebo-controlled study in 340 patients, that will assess safety and tolerability of MaaT033 before and after allo-HSCT, as well as the efficacy of the candidate in improving overall survival and prevention of allo-HSCT complications. The trial initiation is planned by end of 2022. This is in line with the program announced during the Company’s IPO in November 2021, and part of the funding raised during the IPO is allocated to the clinical development of MaaT033.

The Phase 1b CIMON topline data will be presented and discussed by Prof. Mohamad Mohty (Professor at Sorbonne University and Head of the Clinical Hematology and Cellular Therapy Department, Saint-Antoine Hospital, AP-HP, France) during the Company’s upcoming Virtual R&D Day, which will be held on Tuesday June 7, 2022 (register here).

Complete trial results will be submitted for presentation and/or publication in a peer-reviewed forum.

About MaaT033

MaaT033 is an oral, full-ecosystem, off-the-shelf, standardized, pooled-donor, high-richness Microbiome Ecosystem TherapyTM. MaaT033 is designed to restore the gut ecosystem to full functionality to improve clinical outcomes as well as to control adverse events related to conventional treatments for liquid tumors. The capsule formulation facilitates administration while maintaining the high and consistent richness and diversity of microbial species, including anti-inflammatory ButycoreTM species.

On June 2, 2022 Proxygen, a leader in the discovery and development of molecular glue degraders, reported that the company has entered into a strategic multi-year research collaboration and license agreement with Merck (Press release, Proxygen, JUN 2, 2022, View Source [SID1234615419]). Proxygen is eligible to receive up to €495 million ($554 million at the average USD/EUR FX rate of Q1 2022) in continuous R&D funding, upfront and success-based pre-clinical, clinical, regulatory, and commercial milestones, as well as additional royalty payments. Under the terms of the agreement, the companies will jointly identify and develop molecular glue degraders up to a clinical candidate stage.

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"We are incredibly excited to start this long-term collaboration with Merck, a globally recognized player in the pharmaceutical industry that shares our drive towards dynamic innovation for the benefit of patients. The partnership validates the unique potential of Proxygen’s glue degrader platform and strategically leverages our common strengths in the targeted protein degradation field", says Dr. Bernd Boidol, CEO of Proxygen.

Molecular glue degraders re-direct the cell’s own quality control machinery towards disease-causing proteins, inducing their selective and complete elimination. Because of their capability to modulate protein classes that would not be amenable to traditional drug discovery approaches, glue degraders hold the promise of unlocking a large proportion of the undruggable target space and delivering innovative therapies for diseases with high medical need. The lack of scalable discovery strategies has however so far hindered the full exploitation of the clinical potential of molecular glue degraders.

By streamlining and fully integrating cutting-edge genomic, proteomic, and biochemical technologies, Proxygen has successfully developed a highly versatile glue degrader discovery engine. The ligase-agnostic screening approach enables the specific and unbiased identification of molecular glue degraders against difficult-to-drug or completely undruggable targets at large scale. The vast amounts of know-how and data generated in the discovery and chemical optimization of degrader molecules continuously improve the understanding of this novel modality and contribute to Proxygen’s pioneering role in the molecular glue degrader space.

On June 2, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported results of a post-hoc study analysis showing that ES-SCLC patients who received trilaciclib prior to chemotherapy had a lower incidence of single- and multilineage myelosuppressive events—fewer cases of severe neutropenia, severe anemia, and severe thrombocytopenia—compared to patients receiving placebo (Press release, G1 Therapeutics, JUN 2, 2022, View Source [SID1234615418]). Moreover, the proportion of patients who experienced at least one multilineage myelosuppressive event was lower in the trilaciclib arm compared to the placebo arm . The data, derived from a post-hoc analysis of Phase 2 trials, were presented in a poster at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.

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"Myelosuppression is a major toxicity of chemotherapy treatment for patients with extensive-stage small cell lung cancer that often results in chemotherapy dose delays and dose reductions, both of which can compromise clinical outcomes," said Jerome Goldschmidt, M.D., medical oncologist with Blue Ridge Cancer Care in Blacksburg, VA, and lead author of the poster. "Both the patients and the healthcare system at large bear the complications of myelosuppressive events such as neutropenia, anemia, and thrombocytopenia, so it is imperative that we achieve clinically meaningful reductions in myelosuppression in multiple cell lineages and its consequences utilizing novel therapies such as trilaciclib."

In the analysis, the researchers calculated the number of patients who experienced single lineage and multilineage myelosuppressive events as well as the total number of events each person experienced in both first-line and second/third-line chemotherapy settings. Only severe grade events (grade ≥ 3 per the National Cancer Institute) were included in the analysis, and 75 percent of patients were in the first-line setting.

Results of the analysis showed that throughout cycles one through four of first-line therapy, fewer patients treated with trilaciclib experienced single-lineage (neutrophil, red blood cell or platelet lineages) and multilineage myelosuppressive events—and fewer events occurred per person—than patients who received placebo.

Specifically, analyses of the pooled data showed that patients receiving trilaciclib in the first-line setting experienced fewer single-lineage myelosuppressive events, including:

a 75% reduction (56.7% to 14.4%) in severe neutropenia compared to patients receiving placebo
a 50% reduction (17.8% to 8.9%) in severe anemia compared to patients receiving placebo
a 100% reduction (12.2% to 0.0%) in severe thrombocytopenia compared to patients receiving placebo
Additionally, analyses of the pooled data showed that patients receiving trilaciclib in the first-line setting experienced fewer concurrent, multilineage myelosuppressive events, including:

a 100% reduction (2.2% to 0.0%) in concurrent severe anemia, severe neutropenia, severe thrombocytopenia compared to patients receiving placebo.
a 100% reduction (13.3% to 0.0%) in concurrent severe neutropenia and severe thrombocytopenia compared to patients receiving placebo
a 50% reduction (4.4% to 2.2%) in concurrent severe neutropenia and severe anemia compared to patients receiving placebo
a 33% reduction (3.3% to 2.2%) in concurrent severe anemia and severe thrombocytopenia compared to patients receiving placebo
Concurrent events were defined as having two or three lineage-specific myelosuppressive events overlap for at least one day.

The ASCO (Free ASCO Whitepaper) poster, titled, "Impact of Trilaciclib on Multilineage Chemotherapy-Induced Myelosuppression Events in Patients with Extensive-Stage Small-Cell Lung Cancer: Post-Hoc Analyses of Data from Randomized Clinical Trials," can be found here.

About Small Cell Lung Cancer

In the United States, approximately 30,000 small cell lung cancer patients are treated annually. SCLC, one of the two main types of lung cancer, accounts for about 10% to 15% of all lung cancers. SCLC is an aggressive disease and tends to grow and spread faster than NSCLC. It is usually asymptomatic; once symptoms do appear, it often indicates that the cancer has spread to other parts of the body. About 70% of people with SCLC will have cancer that has metastasized at the time they are diagnosed. The severity of symptoms usually increases with increased cancer growth and spread. From the time of diagnosis, the general 5-year survival rate for people with SCLC is 6%. The five-year survival rates for limited-stage (the cancer is confined to one side of the chest) SCLC is 12% to 15%, and for extensive stage (cancer has spread to the other lung and beyond), survival rates are less than 2%. Chemotherapy is the most common treatment for ES-SCLC. A majority (>90%) of ES-SCLC patients receive first-line chemotherapy at the time of treatment initiation.

On June 2, 2022 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (NASDAQ: CRSP) reported new late-breaking clinical data accepted for oral presentation at the 2022 European Hematology Association (EHA) (Free EHA Whitepaper) Congress (Press release, CRISPR Therapeutics, JUN 2, 2022, View Source [SID1234615416]). Vertex also announced three abstracts accepted for poster presentation at EHA (Free EHA Whitepaper).

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Late-breaking abstract #LB2367 entitled "Efficacy and Safety of A Single Dose of CTX001 For Transfusion-Dependent Βeta-Thalassemia and Severe Sickle Cell Disease," will be an oral presentation on Sunday, June 12 at 09:45‑11:15 CEST. The abstract from Vertex and CRISPR Therapeutics includes data on patients treated in CLIMB‑111 and CLIMB‑121 and followed in CLIMB‑131 with CTX001, now known as exagamglogene autotemcel (exa-cel). This abstract has been selected for the media briefing program and is therefore embargoed until Saturday, June 11 at 09:00 am CEST.

In addition, three real-world evidence and health economics abstracts from Vertex have been accepted for poster presentation.

Abstract #P1704 entitled "Projected Lifetime Economic Burden of Severe Sickle Cell Disease in the United States," will be a poster presentation on Friday, June 10 at 16:30‑17:45 CEST. The abstract posted online projects the per-patient lifetime direct health care cost of severe sickle cell disease (SCD) from a U.S. health care payer perspective using an economic model developed based on published model frameworks.

Abstract #P1703 entitled "Economic Burden of Transfusion‑Dependent Beta‑Thalassemia in the United States," will be a poster presentation on Friday, June 10 at 16:30‑17:45 CEST. The abstract posted online estimates the economic burden of transfusion-dependent beta thalassemia (TDT) using administrative claims data to estimate the costs and health care utilization associated with disease management in the U.S.

Abstract #P1482 entitled "Patients With Severe Sickle Cell Disease on Standard-of-Care Treatment Are Very Unlikely to Become VOC‑Free for One Year: A Cohort Study of Medicaid Enrollees," will be a poster presentation on Friday, June 10 at 16:30‑17:45 CEST. The abstract posted online contextualizes the efficacy of exa‑cel in eliminating vaso‑occlusive crises (VOCs) in patients with SCD using nationwide U.S. Medicaid claims data from 2000 to 2014 to assess the proportion of patients with recurrent VOCs who became VOC‑free during a 1‑year follow up on standard of care.
The accepted abstracts are now available online on the EHA (Free EHA Whitepaper) website.

Exa‑cel is being investigated in multiple ongoing clinical trials as a potential one-time therapy for patients with either TDT or SCD.

About exagamglogene autotemcel (exa-cel)

Exa‑cel, formerly known as CTX001, is an investigational, autologous, ex vivo CRISPR/Cas9 gene‑edited therapy that is being evaluated for patients with TDT or SCD characterized by recurrent VOCs, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen‑carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa‑cel has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, exa‑cel has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene‑editing approaches being evaluated for TDT and SCD, exa‑cel is the furthest advanced in clinical development.

About CLIMB‑111 and CLIMB‑121

The ongoing Phase 1/2/3 open‑label trials, CLIMB‑111 and CLIMB‑121, are designed to assess the safety and efficacy of a single dose of exa‑cel in patients ages 12 to 35 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now closed for enrollment. Patients will be followed for approximately two years after exa‑cel infusion. Each patient will be asked to participate in CLIMB‑131, a long‑term follow‑up trial.

About CLIMB-131

This is a long‑term, open‑label trial to evaluate the safety and efficacy of exa‑cel in patients who received exa‑cel in CLIMB‑111, CLIMB‑121, CLIMB‑141 or CLIMB‑151. The trial is designed to follow participants for up to 15 years after exa‑cel infusion.

About CLIMB‑141 and CLIMB‑151

The ongoing Phase 3 open-label trials, CLIMB‑141 and CLIMB‑151, are designed to assess the safety and efficacy of a single dose of exa‑cel in patients ages 2 to 11 years with TDT or with SCD, characterized by recurrent VOCs, respectively. The trials are now open for enrollment and currently enrolling patients ages 5 to 11 years of age and will plan to extend to ages 2 to less than 5 years of age at a later date. Each trial will enroll up to 12 patients. Patients will be followed for approximately two years after infusion. Each patient will be asked to participate in CLIMB-131, a long‑term follow‑up trial.

About the Gene‑Editing Process in These Trials

Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, exa‑cel, will then be infused back into the patient as part of an autologous hematopoietic stem cell transplant (HSCT), a process which involves a patient being treated with myeloablative busulfan conditioning. Patients undergoing HSCT may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of exa‑cel. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of exa‑cel on multiple measures of disease and for safety.

About the Vertex‑CRISPR Collaboration

Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. Exa‑cel represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing and commercialization of exa‑cel and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics.

On June 2, 2022 Sysmex Inostics, Inc. and QIAGEN N.V. reported that it will co-exhibit at the 2022 ASCO (Free ASCO Whitepaper) Annual Meeting, the world’s largest clinical cancer research meeting, held June 3, 2022, through June 7, 2022, in Chicago (Press release, Sysmex Inostics, JUN 2, 2022, View Source [SID1234615415]).

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QIAGEN, the leading global provider of sample to insight solutions for molecular testing, and Sysmex Inostics combined forces in July 2021 to accelerate global companion diagnostic access. QIAGEN provides unparalleled global custom cancer companion diagnostics (CDx) development and commercialization capabilities utilizing Sysmex Inostics ultra-sensitive NGS liquid biopsy technology. The goal of the alliance is to promote early clinical implementation of Sysmex Inostics’ technology to expedite clinical trial timelines for pharmaceutical companies that develop molecularly targeted drugs for cancer.

"Sysmex Inostics is focused on developing tools to support the fight against cancer and other devastating diseases. By partnering with industry leaders like QIAGEN we can help accelerate the fight to help patients with these diseases," said Shinichi Sato, CEO of Sysmex Inostics, Inc. "We look forward to highlighting our partnership with QIAGEN at ASCO (Free ASCO Whitepaper) 2022."

"Through our partnership with Sysmex, we can develop ultrasensitive blood-based NGS panels to the specific requirements of our pharma partners for their clinical trials," stated Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics of QIAGEN. Arnold added, "If and when a CDx is required, QIAGEN will lead IVD submission, manufacturing, and global commercialization as a kitted product."

Sysmex and QIAGEN will highlight their alliance at ASCO (Free ASCO Whitepaper) booth 8149, Saturday, June 4, 2022, through Monday, June 6, 2022, 9:00 AM – 5:00 PM CDT each day.

Poster Presentations Utilizing Sysmex Inostics’ Technology
Yoshinori Kagawa MD, PhD, Department of Gastroenterological Surgery, Osaka General Medical Center, Osaka, Japan, will present the poster "Plasma RAS dynamics and anti-EGFR rechallenge efficacy in patients with RAS/BRAF wild-type metastatic colorectal cancer: REMARRY and PURSUIT trials." Circulating tumor DNA (ctDNA) was analyzed and monitored using the Sysmex Inostics OncoBEAMTM RAS CRC Kit. Dr. Kagawa will present poster 3518 during the Gastrointestinal Cancer—Colorectal and Anal session on Saturday, June 4, 2022, 3:00 PM-4:30 PM CDT.

Linda (Yilin) Cao, MD, Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, will present the poster "Dynamic cell free HPV DNA is an early measure of treatment responsiveness in patients receiving induction chemotherapy for HPV-related head and neck cancer." Findings add to the breadth of ongoing clinical studies using HPV-SEQ to investigate de-escalation of HPV-positive patients from unnecessary and potentially harmful head and neck squamous cell carcinomas (HNSCC) treatments. HPV-SEQ is an ultrasensitive test for the detection of HPV16/18 DNA from blood and is CLIA validated to detect as few as five HPV DNA molecules from two tubes of blood.1 See here for additional study information. Dr. Cao will present poster 6062 during the Head and Neck Cancer session on Monday, June 6, 2022, 1:15 PM- 4:15 PM CDT.