On January 17, 2022 MaaT Pharma (EURONEXT: MAAT – the "Company"), a French clinical-stage biotech and a pioneer in the development of microbiome-based ecosystem therapies dedicated to improving survival outcomes for patients with cancer, reported business objectives and clinical milestones for 2022(Press release, MaaT Pharma, JAN 17, 2022, View Source [SID1234605510]).

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"Despite the ongoing pandemic, 2021 was a turning point in MaaT Pharma history, as we became the first microbiome therapeutic company to be listed on Euronext, we established a Phase 2 proof of concept with MaaT013 in acute Graft-vs-Host-Disease, and we expanded our hemato-oncology program with the initiation of a Phase 1b trial of MaaT033, our oral formulation," stated Hervé Affagard, CEO and co-founder of MaaT Pharma. "We expect new achievements in 2022, with 3 clinical programs either ongoing or starting. This year should see key clinical milestones in hemato-oncology with MaaT013 ready to enter Phase 3 and new clinical data for MaaT033 expected in the first half of 2022. Moreover, our immuno-oncology program leveraging a new generation of products, MaaT03X to address solid tumors, is currently in nonclinical validation. Since our creation, we have been pioneering the development of Microbiome Ecosystem Therapies to bring these innovations to millions of patients fighting cancer globally."

Expected milestones in 2022

Hemato-oncology– Clinical programs:

MaaT013 for the treatment of aGvHD (Orphan Drug Designation by the FDA and the EMA):

MaaT013 is a full-ecosystem, off-the-shelf, standardized, pooled-donor Microbiome Ecosystem Therapy for enema administration.
MaaT013 is ready to start its pivotal Phase 3 in Europe. MaaT Pharma has already received regulatory authorization to start this trial in France and Germany. The Company will communicate upon the inclusion of the first patient (FPI).
The initiation of the clinical trials for MaaT013 in the United States will depend on the outcome of ongoing exchanges with the Food and Drug Administration (FDA) in response to the August 2021 clinical hold letter regarding the IND for MaaT013 in the US.
MaaT013 has been successfully evaluated in Phase 2 clinical trial in patients with steroid-resistant grade III-IV gastro-intestinal (GI) aGvHD as well as in an ongoing compassionate use program (EAP) in France in patients with Grade II-IV GI-aGvHD having failed previous therapies, with promising results.
To date, more than 100 patients with aGvHD have been safely treated with MaaT013, including:
24 patients in the Phase 2 trial.
96 patients in the Early Access Program in France (EAP). This program has also been an opportunity for the Company to strengthen its supply chain and manufacturing capacities to deliver MaaT013 regularly and safely to 18 hospital transplant centers as of today.
Additionally, MaaT Pharma has recently honored two requests for compassionate use of MaaT013 originating from two other European countries.

MaaT033 for the prevention of complications due to allogeneic hematopoietic stem cell transplantation (allo-HSCT)

MaaT033 is a donor-derived, standardized, high-richness, high-diversity Microbiome Ecosystem Therapy for oral administration.
MaaT033, is currently being evaluated to define dose regimen in a Phase 1b clinical trial in patients with acute myeloid leukemia (AML) following intensive chemotherapy.
There have been 4 meetings of an independent safety review Board (DSMB) to date evaluating the safety of the trial and that concluded in support of the continuation of the study.
In Q1 2022, the Company will provide interim results of engraftment data for the Phase 1b clinical trial.
Complete results are expected in the first half of 2022 and a pivotal Phase 2/3 may be initiated at the end of 2022 to evaluate MaaT033 as a prophylactic treatment for blood cancer patients undergoing allo-HSCT.

Immuno-oncology – Clinical and nonclinical programs

MaaT013 for the improvement of a patient’s response to Immune Checkpoint Inhibitors (ICI) –proof of concept clinical trial sponsored by AP-HP

MaaT013 is ready to enter a randomized, placebo-controlled Phase 2a trial to evaluate its effect on the efficacy of ICI treatment in patients with metastatic melanoma. AP-HP is the sponsor of this trial. MaaT Pharma will supply the drugs and perform the microbiome profiling of patients using its proprietary gutPrint platform.
French regulatory authorities have approved the trial and the Company will communicate upon inclusion of the first patient.
MaaT03X for the increase in the response rate to Immune Checkpoint Inhibitors in patients with solid tumors

MaaT03X is a fermented, high diversity, rationally designed Microbiome Ecosystem Therapy for oral administration. MaaT03X’s design is based on clinical and microbiome data analyses from hundreds of patients.
MaaT Pharma is leveraging its proprietary gutPrint computational biology platform and full ecosystem co-fermentation technology to develop this new generation of candidates.
The first MaaT03X candidate is currently in nonclinical testing and will aim to improve the anti-cancer efficacy of ICI in patients with an undisclosed solid tumor with a high unmet need. A first clinical study is expected to start in the first half of 2023.
In 2021, the MaaT03X program received a €1.9M grant to support industrialization of the manufacturing process.

cGMP manufacturing facilities

MaaT Pharma has entered negotiations with a potential partner to secure the expansion of the Company’s cGMP manufacturing capacities, as stated in a letter of intent signed in November 2021. A new cGMP manufacturing plant, entirely dedicated to the Company’s high-diversity and high-richness Microbiome Ecosystem Therapies, would be built in the Auvergne-Rhône-Alpes region allowing the Company to operate its own equipment and processes while benefitting from full associated cGMP services provided by the partner. Contracting is expected to take place in H1 2022.

Initiation of coverage of MaaT Pharma stock

To date, three brokerage firms have initiated coverage of MaaT Pharma (EURONEXT: MAAT):

2021 – KBC Securities: research report "More than a Gut Feeling"
2021 – Kempen: research report "No Guts no Glory"
Jan 2022 – Portzamparc / Groupe BNP Paribas: research report "Échec et MaaT pour le cancer"

2022 Financial calendar

February 28, 2022 – Revenues and Cash Position as of December 31st, 2021
April 15, 2022 – Annual Results 2021
May 05, 2022 – Revenues and Cash Position Quarter 1
May 23, 2022 – General Meeting
July 28, 2022 – Revenues and Cash Position Quarter 2
September 29, 2022 – Half-year Results (April – September)
November 08, 2022 – Revenues and Cash Position Quarter 3

On January 17, 2022 Tyligand Bioscience, a clinical-stage biotechnology company developing innovative small-molecule therapeutics against drug resistant cancers, reported that its investigational new drug (IND) application of TSN084 has been approved by China’s National Medical Products Administration (NMPA) (Press release, Tyligand Bioscience, JAN 17, 2022, View Source [SID1234644991]).

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TSN084 is a first-in-class phosphorylation inhibitor targeting CDK8/19 and several other kinases implicated in tumorigenesis and immune evasions. Phase I enrollment will be conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences and other clinical centers. In Oct 2021, the company has received IND approval from the US FDA for the experimental drug and dose escalation studies are expected to commence soon.

Dr. Tony Zhang, cofounder and CEO of Tyligand Bioscience, commented, "We are excited about this important milestone and the potential of TSN084 for helping patients with tough to treat tumors. Accomplishing this goal is testimonial to the quality and speed of the Tyligand team at transforming novel molecules into quality drug candidates. It is an important step toward testing our approach of selective and simultaneous inhibition of multiple factors responsible for the major hallmarks of cancer."

On January 17, 2022 Aclys Bio Corp ("Aclys"), a company discovering and developing precision biologics for the treatment of cancer, earlier this month reported a new exclusive research and commercial license option agreement with Genmab A/S (Nasdaq: GMAB), an international biotech company specializing in the creation and development of differentiated antibody therapeutics for the treatment of cancer (Press release, Virtici, JAN 17, 2022, View Source [SID1234608857]).

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Under the terms of the agreement, Genmab secures exclusive rights to Aclys antibodies (specific to an undisclosed target) for further research in conjunction with Genmab’s proprietary platforms. Genmab is also granted the option to advance development and commercialization of resulting products.

Aclys has built a broad range of antibodies using its PILA platform to create targeted therapeutics for solid tumors. The agreement with Genmab recognizes the capability of the Aclys PILA platform to identify novel precision targets.

"We have differentiated, high value targets, unique antibody engineering capabilities, and a team that has delivered some of the most valuable monoclonal antibodies currently in development.", said Dr. Tony Cooper, Aclys Cofounder and CEO. "This agreement with Genmab is integral to advancing our goal of delivering life-saving therapies to patients." Aclys is a leader in the emerging field of precision immune medicine. Aclys utilizes a proprietary set of patient molecular data to select differentiated targets and create precision biologics with the safety profile and response rates only achievable with precision biologics.

On January 18, 2022 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) reported that the Company has entered into a drug discovery collaboration with Eli Lilly and Company ("Lilly") in the field of metabolic diseases with a focus on kidney diseases and diabetes (Press release, Evotec, JAN 17, 2022, View Source [SID1234605514]).

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The collaboration leverages Evotec’s extensive experience and track record of delivering in the field of metabolic diseases, as well as its unique and extensive kidney disease patient database, to identify and validate promising novel targets for therapeutic intervention. Evotec will be responsible for the discovery of potential drug candidates for the treatment of diabetes and chronic kidney diseases from targets identified by Lilly or by Evotec. Lilly reserves the right to select up to five programmes developed within this partnership and to continue with any subsequent development, clinical validation and commercialisation.

The collaboration initially runs for a term of three years. In addition to an undisclosed upfront payment, Evotec will be eligible to receive success-based discovery development, regulatory and commercial milestone payments of up to US$ 180 m per programme, as well as tiered royalties on net sales of any products resulting from the collaboration, for a potential overall value up to US$ 1 bn.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, commented: "We are excited to enter into this research partnership with Lilly. Over a period of several years, Evotec has systematically built a proprietary patient database by conducting multi-omics analyses of biospecimens from patient biobanks covering metabolic and kidney diseases. Evotec’s patient-derived molecular data in combination with our omics-supported multimodality drug discovery platform delivers highest quality drug candidates for our partners. We are proud to collaborate with Lilly in diabetes and kidney diseases as they are one of the leading companies in these areas.

On January 17, 2022 AstraZeneca and Daiichi Sankyo reported that they have received notification of acceptance of the supplemental Biologics License Application (sBLA) of Enhertu (trastuzumab deruxtecan) for the treatment of adult patients in the US with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen. The application has also been granted Priority Review (Press release, AstraZeneca, JAN 17, 2022, View Source [SID1234605502]).

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Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by AstraZeneca and Daiichi Sankyo.

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision, is during the second quarter of 2022.

The sBLA is being reviewed under the Real-Time Oncology Review (RTOR) programme and Project Orbis, two initiatives of the FDA which are designed to bring effective cancer treatments to patients as early as possible. RTOR allows the FDA to review components of an application before submission of the complete application. Project Orbis provides a framework for concurrent submission and review of oncology medicines among participating international partners.

Breast cancer is the most common cancer worldwide, with more than two million cases diagnosed in 2020, resulting in nearly 685,000 deaths globally.2 Approximately one in five cases of breast cancer are considered HER2-positive.3 Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.4 More treatment options are needed to further delay progression and extend survival.4-6

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca said: "This review across geographies and the Priority Review in the US as part of Project Orbis is so important because it speaks to the transformative potential of Enhertu based on the unprecedented progression-free survival benefit in this setting. The news reinforces the importance of bringing this potential new option to patients as quickly as possible."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "This regulatory review of Enhertu in the US marks the first time this medicine is participating in both the Real-Time Oncology Review and Project Orbis programmes. The FDA’s prioritisation of our application underscores the potential of this medicine and the continued need to expedite the availability of new treatment options, while making it possible to potentially receive approvals in several countries concurrently."

The sBLA is based on data from the DESTINY-Breast03 trial presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021.

In the trial, Enhertu demonstrated a 72% reduction in the risk of disease progression or death compared to T-DM1 (hazard ratio [HR] 0.28; 95% confidence interval [CI]: 0.22-0.37; p=7.8×10-22) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

DESTINY-Breast03 also recorded that nearly all patients treated with Enhertu during the trial were alive at one year (94.1%) compared to 85.9% of patients treated with T-DM1. Confirmed objective response rate (ORR) more than doubled in the Enhertu arm versus the T-DM1 arm (79.7% vs. 34.2%). The safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.

In September 2021, Enhertu received its fourth Breakthrough Therapy Designation (BTD) in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens.

Enhertu is approved for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in more than 30 countries based on the results from the DESTINY-Breast01 trial.

Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.

Notes

HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths in women worldwide.2 More than two million patients with breast cancer were diagnosed in 2020, resulting in nearly 685,000 deaths globally.2 Approximately one in five cases of breast cancer are considered HER2-positive.3

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8

Despite initial treatment with trastuzumab and a taxane, people with HER2-positive metastatic breast cancer will often experience disease progression.4 More treatment options are needed to further delay progression and extend survival.4-6

DESTINY-Breast03
DESTINY-Breast03 is a global head-to-head, randomised, open-label, registrational Phase III trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints include overall survival, ORR, duration of response, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial. A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received one or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast03 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial. A Type II Variation is currently under review by the EMA for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior anti-HER2-based regimen.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Enhertu was highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the "ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers," based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2-mutated cohort of the DESTINY-Lung01 trial.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (referred to as Daiichi Sankyo) and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option for metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.