On December 14, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from the phase III POLARIX study showing that treatment with Polivy (polatuzumab vedotin) in combination with MabThera/Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) significantly reduced the risk of disease progression, relapse or death (progression-free survival; PFS) by 27% compared with the current standard-of-care, MabThera/Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, Hoffmann-La Roche, DEC 14, 2021, View Source [SID1234597063]). Safety outcomes were consistent with those seen in previous trials and the safety profile was comparable for Polivy plus R-CHP versus R-CHOP.1,2 Results were presented as a late-breaking abstract and during a press briefing at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Tuesday, December 14, 2021. Data from POLARIX were simultaneously published in the New England Journal of Medicine (NEJM). The study is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

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"As many as 40% of people with this aggressive lymphoma experience a return of their cancer after initial therapy, at which point they face a poor prognosis and limited treatment options," said Levi Garraway, M.D., Ph.D., Chief Medical Officer and Head of Global Product Development. "This Polivy-based regimen may conceivably change the disease course for many people with DLBCL, so we are working with health authorities around the world to make this important, potential new treatment option available as soon as possible."

"DLBCL is an aggressive disease and, despite continuous research efforts, there have been limited treatment advances in the frontline setting in the past 20 years," said Professor Hervé Tilly, POLARIX Principal Investigator and Professor of Haematology at the University of Rouen. "Results from the POLARIX trial represent an important advancement, bringing hope to people with this disease."

First efficacy and safety data from the pivotal phase III POLARIX study showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP in patients with previously untreated DLBCL after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; P<0.02).1,2 PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goals of first-line therapy: avoiding disease relapse, disease progression, and death. The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%), respectively.1,2 The POLARIX data form the basis of ongoing marketing applications to global health authorities.

Currently Polivy is used as an off-the-shelf, fixed-duration treatment option in the relapsed or refractory (R/R) DLBCL setting and is approved in combination with bendamustine and MabThera/Rituxan for the treatment of R/R DLBCL in more than 70 countries worldwide, including in the EU and in the United States. Roche continues to explore areas of unmet need where Polivy has the potential to deliver benefit, with ongoing studies investigating combinations of Polivy with the CD20xCD3 T-cell engaging bispecific antibodies mosunetuzumab and glofitamab, with Venclexta/Venclyxto (venetoclax), which is being developed by AbbVie and Roche, and with MabThera/Rituxan in combination with gemcitabine and oxaliplatin in the phase III POLARGO study.

Follow Roche on Twitter via @Roche and keep up to date with ASH (Free ASH Whitepaper) 2021 news and updates by using the hashtag #ASH21.

About the POLARIX study
POLARIX [NCT03274492] is an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy (polatuzumab vedotin) plus MabThera/Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus MabThera/Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma. Eight-hundred and seventy-nine patients were randomised 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by MabThera/Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of MabThera/Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About the LYSA and the LYSARC
The Lymphoma Study Association, or LYSA, is the internationally leading cooperative group for lymphoma research in Europe, conducting clinical studies ranging from the first tests of new medicines in humans to the establishment of reference therapeutic strategies. LYSA includes in its network more than 120 care centres distributed throughout three countries (France, Belgium, Portugal), and collaborates with many scientific teams at the international level.

The Lymphoma Academic Research Organisation, or LYSARC, is the LYSA operational structure that conducts clinical research projects on lymphomas at the international level.

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma, making it a promising target for the development of new therapies.3,4 Polivy binds to cancer cells such as CD79b and kills these B-cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells.5,6 Polivy is being developed by Roche using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL. Polivy is marketed in the US by Genentech as Polivy (polatuzumab vedotin-piiq), with piiq as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. Food and Drug Administration.

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is the most common form of non-Hodgkin lymphoma (NHL), accounting for about one in three cases of NHL.7 DLBCL is an aggressive (fast-growing) type of NHL.8 While it is generally responsive to treatment in the frontline, as many as 40% of patients will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.8 Approximately 150,000 people worldwide are estimated to be diagnosed with DLBCL each year.9

About Roche in haematology
Roche has been developing medicines for people with malignant and non-malignant blood diseases for over 20 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera/Rituxan (rituximab), Gazyva/Gazyvaro (obinutuzumab), Polivy (polatuzumab vedotin), Venclexta/Venclyxto (venetoclax) in collaboration with AbbVie, and Hemlibra (emicizumab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibodies, glofitamab and mosunetuzumab, targeting both CD20 and CD3, and cevostamab, targeting both FcRH5 and CD3; Tecentriq (atezolizumab), a monoclonal antibody designed to bind with PD-L1; and crovalimab, an anti-C5 antibody engineered to optimise complement inhibition. Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further.

On December 14, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported two data presentations, highlighted data from the UNITY-CLL Phase 3 trial evaluating the combination of ublituximab, the Company’s investigational anti-CD20 monoclonal antibody and UKONIQ (umbralisib), the Company’s inhibitor of PI3K-delta and CK1-epsilon, (U2), in patients with both treatment naïve and relapsed or refractory chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, DEC 14, 2021, View Source [SID1234597087]). Data presentations occurred yesterday evening during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "We are pleased to share two presentations last night at the ASH (Free ASH Whitepaper) annual meeting which included additional analyses of the UNITY-CLL Phase 3 trial evaluating the U2 combination in patients with both treatment naïve and relapsed or refractory CLL. We believe these presentations showcase the versatility of the U2 combination both by treatment subgroup, and also interestingly in a patient population generally characterized as unsuitable for BTKi-based therapy. While significant advances have been made in the treatment of CLL, there still remains underserved patients who may not be good candidates for or fail to respond to currently available treatments."

PRESENTATION HIGHLIGHTS

Poster Presentation Title: Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study

A total of 210 CLL patients were enrolled in the U2 cohort of the UNITY-CLL trial, including 119 treatment naïve and 91 previously treated.
Efficacy and safety highlights for the treatment naïve (TN) population included:
Independent review committee (IRC) assessed progression-free survival (PFS) of U2 in the TN population was 38.5 months, with two-year PFS of 76.6%
84% IRC-assessed overall response rate (ORR) in the TN population, including 5% complete response (CR)/complete response with incomplete marrow recovery (CRi)
Responses were durable with 76% maintaining response at 2 years
Grade 3/4 adverse events (AEs) of special interest occurring in the TN population included ALT elevation (12%), AST elevation (8%), rash (3%), pneumonia (7%), non-infectious colitis (3%), pneumonitis (1%) and opportunistic infections (1%).
Efficacy and safety highlights for the previously treated population (PT) included:
IRC-assessed PFS in the PT population was 19.5 months, with two-year PFS of 41.3%
82% IRC-assessed ORR in the PT population, including 4% CR/CRi
Responses were durable, with 43% maintaining response at 2 years
Grade 3/4 adverse events (AEs) of special interest occurring in the PT population included ALT elevation (3%), AST elevation (2%), rash (1%), pneumonia (11%) and opportunistic infections (1%).
Poster Presentation Title: Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

A total of 210 CLL patients were enrolled in the U2 cohort of the UNITY-CLL trial, including 119 treatment naïve and 91 previously treated.
131 (64%) of U2 treated patients had at least 1 comorbid condition or concomitant medication (conmed) that could pose potential issues with BTKi therapy.
88% ORR, including 5% CR, for those patients with at least 1 comorbidity or conmed (n=131), compared to 83% ORR, including 5% CR, for the entire U2 population (n=210).
No difference in IRC-assessed PFS was observed between the group of patients with at least 1 comorbidity or conmed compared to the entire U2 population (31.9 months for both groups).
Grade 3/4s AEs of clinical interest in the group of patients with at least 1 comorbidity or conmed and the entire U2 population respectively, included ALT elevation (8%, 8%), AST elevation (4%, 5%), non-infectious colitis (3%, 2%) and pneumonitis (1%, 0.5%).
The above referenced presentations are now available on the Publications page of the Company’s corporate website at View Source

On December 14, 2021 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported results from the Phase III POLARIX study showing that treatment with Polivy (polatuzumab vedotin) in combination with Rituxan (rituximab) plus cyclophosphamide, doxorubicin and prednisone (R-CHP) significantly reduced the risk of disease progression, relapse or death (progression-free survival; PFS) by 27% compared with the current standard-of-care, Rituxan plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Safety outcomes were consistent with those seen in previous trials, and the safety profile was comparable for Polivy plus R-CHP versus R-CHOP (Press release, Genentech, DEC 14, 2021, View Source [SID1234597131]). Results were presented as a late-breaking abstract and during a press briefing at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition on Tuesday, December 14, 2021. Data from POLARIX were simultaneously published in the New England Journal of Medicine (NEJM).

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"As many as 40% of people with this aggressive lymphoma experience a return of their cancer after initial therapy, at which point they face a poor prognosis and limited treatment options," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "This Polivy-based regimen may conceivably change the disease course for many people with DLBCL, so we are working with health authorities around the world to make this important, potential new treatment option available as soon as possible."

"DLBCL is an aggressive disease and, despite continuous research efforts, there have been limited treatment advances in the frontline setting in the past 20 years," said Professor Hervé Tilly, POLARIX principal investigator and professor of hematology at the University of Rouen. "Results from the POLARIX trial represent an important advancement, bringing hope to people with this disease."

First efficacy and safety data from the pivotal Phase III POLARIX study showed a significant improvement in PFS with Polivy plus R-CHP versus R-CHOP in patients with previously untreated DLBCL after a median follow-up of 28.2 months (hazard ratio [HR] 0.73; 95% confidence interval [CI]: 0.57–0.95; p<0.02). PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goals of first-line therapy: avoiding disease relapse, disease progression and death. The safety profile was comparable for Polivy plus R-CHP versus R-CHOP, including rates of Grade 3-4 adverse events (AEs; 57.7% versus 57.5%), serious AEs (34.0% versus 30.6%), Grade 5 AEs (3.0% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13.0%). The POLARIX data form the basis of ongoing marketing applications to global health authorities.

Currently, Polivy is used as an off-the-shelf, fixed-duration treatment option in the relapsed or refractory (R/R) DLBCL setting and is approved in combination with bendamustine and Rituxan for the treatment of R/R DLBCL in more than 70 countries worldwide, including in the EU and in the United States. Genentech continues to explore areas of unmet need where Polivy has the potential to deliver benefit, with ongoing studies investigating combinations of Polivy with the CD20xCD3 T-cell engaging bispecific antibodies mosunetuzumab and glofitamab, with Venclexta (venetoclax), which is being developed by AbbVie and Genentech, and with Rituxan in combination with gemcitabine and oxaliplatin in the Phase III POLARGO study.

Follow Genentech on Twitter via @Genentech and keep up to date with ASH (Free ASH Whitepaper) 2021 news and updates by using the hashtag #ASH21.

About the POLARIX study
POLARIX [NCT03274492] is an international Phase III, randomized, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy (polatuzumab vedotin) plus Rituxan (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) versus Rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in people with previously untreated diffuse large B-cell lymphoma (DLBCL). Eight-hundred and seventy-nine patients were randomized 1:1 to receive either Polivy plus R-CHP plus a vincristine placebo for six cycles, followed by Rituxan for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituxan. The primary outcome measure is progression-free survival as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma. POLARIX is being conducted in collaboration with The Lymphoma Study Association (LYSA) and The Lymphoma Academic Research Organisation (LYSARC).

About Polivy (polatuzumab vedotin-piiq)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed specifically in the majority of B cells, an immune cell impacted in some types of non-Hodgkin’s lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimize the effects on normal cells. Polivy is being developed by Genentech using Seagen ADC technology and is currently being investigated for the treatment of several types of NHL.

Polivy U.S. Indication
Polivy is a prescription medicine used with other medicines, bendamustine and a rituximab product, to treat diffuse large B-cell lymphoma in adults who have progressed after at least two prior therapies.

The accelerated approval of Polivy is based on a type of response rate. There are ongoing studies to confirm the clinical benefit of Polivy.

Important Safety Information
Possible serious side effects
Everyone reacts differently to Polivy therapy, so it’s important to know what the side effects are. Some people who have been treated with Polivy have experienced serious to fatal side effects. A patient’s doctor may stop or adjust a patient’s treatment if any serious side effects occur. Patients must contact their healthcare team if there are any signs of these side effects.

Nerve problems in arms and legs: This may happen as early as after the first dose and may worsen with every dose. If a patient already has nerve pain, Polivy may make it worse. The patient’s doctor will monitor for signs and symptoms, such as changes in sense of touch, numbness or tingling in hands or feet, nerve pain, burning sensation, any muscle weakness, or changes to walking patterns
Infusion-related reactions: A patient may experience fever, chills, rash, breathing problems, low blood pressure, or hives within 24 hours of the infusion
Infections: Patients should contact their healthcare team if they experience a fever of 100.4°F or higher, chills, cough, or pain during urination. Also, a patient’s doctor may give medication before giving Polivy, which may prevent some infections, and monitor blood counts throughout treatment with Polivy. Treatment with Polivy can cause severe low blood cell counts
Rare and serious brain infections: A patient’s doctor will monitor the patient closely for signs and symptoms of these types of infections. Patients should contact their doctor if they experience confusion, dizziness or loss of balance, trouble talking or walking, or vision changes
Tumor lysis syndrome: Caused by the fast breakdown of cancer cells. Signs include nausea, vomiting, diarrhea, and lack of energy
Potential harm to liver: Some signs include tiredness, weight loss, pain in the abdomen, dark urine, and yellowing of the skin or the white part of the eyes. Patients may be at higher risk if they already have liver problems or are taking other medication
Side effects seen most often
The most common side effects during treatment were:

Low blood cell counts (platelets, red blood cells, white blood cells)
Nerve problems in arms and legs
Tiredness or lack of energy
Diarrhea
Nausea
Fever
Decreased appetite
Infections
Polivy may not be for everyone. A patient should talk to their doctor if they are:

Pregnant or may be pregnant: Data have shown that Polivy may harm an unborn baby
Planning to become pregnant: Women should avoid getting pregnant while taking Polivy. Women should use effective contraception during treatment and for at least 3 months after their last Polivy treatment. Men taking Polivy should use effective contraception during treatment and for at least 5 months after their last Polivy treatment
Breastfeeding: Women should not breastfeed while taking Polivy and for at least 2 months after the last dose
These may not be all the side effects. Patients should talk to their healthcare provider for more information about the benefits and risks of Polivy treatment.

On December 14, 2021 Gretel.ai reported a collaboration with Illumina, Inc. (NASDAQ: ILMN), the global leader in DNA sequencing and array-based technologies, to create privacy-protected, synthetic genomic data that can be accessed by medical researchers anywhere (Press release, Illumina, DEC 14, 2021, View Source [SID1234597167]). This announcement includes the release of a successful study the partnership conducted, which proves the viability of significant new use cases for synthetic data in genomics and related fields including medical diagnosis, biotechnology, forensic biology, virology, and biological systematics. Beyond healthcare and life sciences, synthetic data has already proven effective in privacy-related use cases in other industries, such as finance and gaming, to help augment small data collections and balance biased datasets.

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This strategic partnership will provide healthcare and life science practitioners access to highly statistically accurate, artificial versions of complex genomic datasets that align with GDPR, CCPA, and other major privacy laws. By using synthetic data, researchers can gain access to datasets immediately and avoid lengthy approval processes by institutional review boards (IRBs) that can take anywhere from 6 months to a year today. "We’re thrilled to show what the highest quality synthetic data available can enable when combined with the groundbreaking genomic work of Illumina’s team," said Ali Golshan, co-founder and CEO of Gretel.

This privacy-preserving method of sharing sensitive data will also allow a much more accelerated and collaborative approach to next-generation DNA sequencing analysis — leading to the discovery of new drugs, insights into genetic disorders, and disease detection and treatments, which could be used for variants of COVID-19, for example. "This work will inspire new medical discoveries and breakthroughs, and has the potential to help save millions of lives as well as improve the quality of life for generations to come," said Alex Watson, co-founder and lead Gretel researcher on the partnership study.

On December 14, 2021 Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplants to more patients, reported that three presentations made at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Magenta Therapeutics, DEC 14, 2021, View Source [SID1234597064]).

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Stem Cell Mobilization: ASH (Free ASH Whitepaper) Presentation and Clinical Development Plans

The data from an investigator-initiated Phase 2 clinical trial in multiple myeloma, presented on December 13, 2021, at the ASH (Free ASH Whitepaper) Annual Meeting and previously reported in a Magenta press release on November 4, 2021, confirmed that MGTA-145 plus plerixafor (i) achieved the primary endpoint for collection of hematopoietic stem cells (HSCs), (ii) was well-tolerated and (iii) mobilized HSCs which were able to successfully engraft with positive 100-day outcomes. The data continue to support MGTA-145 plus plerixafor as a potentially compelling combination with complementary mechanisms of action.

Building upon the encouraging cell collection data from the Phase 2 investigator-initiated trial, Magenta plans to pursue a company-sponsored Phase 2 clinical trial in healthy subjects to further increase cell collection yield through adjustments of the dosing and administration regimen. This is a capital-efficient approach designed to enable expedited enrollment, flexibility in execution and reduced patient variability which will inform planned clinical trial evaluations in multiple myeloma patients and allogeneic stem cell transplant. Magenta will close its current allogeneic clinical trial while continuing to advance its MGTA-145 clinical trial in sickle cell disease in partnership with bluebird bio due to the predicted pharmacology of MGTA-145 and plerixafor in the sickle cell patient setting for HSC gene therapy.

"We believe the current profile of MGTA-145 plus plerixafor, with enhanced cell collection yield, could provide significant clinical benefit to patients and favorably position the product commercially," said Jeff Humphrey, M.D., Chief Medical Officer, Magenta Therapeutics. "We believe there are dosing and administration adjustments that could further improve cell collection and also expect that this proposed clinical trial will answer key clinical questions which could, ultimately, be major differentiators for the program moving forward."

Targeted Conditioning: ASH (Free ASH Whitepaper) Presentations and Phase 1/2 Clinical Trial

Two presentations relating to Magenta’s MGTA-117 targeted conditioning program were made on December 11-12, 2021, at the ASH (Free ASH Whitepaper) Annual Meeting. The first was an oral presentation of non-human primate data supporting the use of a CD117-targeted ADC to condition for HSC gene therapy. The second was a poster presentation of preclinical mouse data that supports the use of a CD117-targeted ADC in combination with lymphodepletion to condition prior to allogeneic HSC transplant. The results from these two presentations were previously disclosed in a press release by Magenta on November 4, 2021.

Gene Therapy. In support of using a CD117-targeted conditioning ADC in gene therapy, Dr. Naoya Uchida, staff scientist at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH), presented preclinical data generated using a tool CD117-targeted ADC in a clinically relevant and fully immune-competent primate gene therapy model for sickle cell disease. The data was generated as part of an NIH-funded (Grant No. HL006008), joint-research collaboration between Magenta and the NIH. The tool CD117-ADC uses the same antibody and engineering as MGTA-117, and although it utilizes a different payload, the results validate CD117 as a target for ADC-based conditioning because of (i) the value of the ADC’s selectivity to the CD117-expressing hematopoietic stem cells and (ii) the effective cell depletion following delivery of an on-target, cell-killing payload. In primates, a single dose of CD117-ADC led to >99% depletion of stem cells, a reduction previously only achieved by four daily doses of busulfan chemotherapy. The data also showed successful engraftment of gene-modified cells with robust and durable fetal hemoglobin levels.

Magenta’s MGTA-117 clinical candidate uses an amanitin payload which has been shown preclinically to be a potent agent for stem cell depletion. Potent stem cell depletion is critical to making room in the bone marrow for engraftment of the modified cells used in gene therapy (and non-modified stem cells used in transplantation). Importantly, depleting CD117-expressing hematopoietic stem cells in a gene therapy setting may allow for the elimination of busulfan, other chemotherapies and irradiation and their known off-target and damaging adverse effects.

"The results suggest that a single dose of a CD117-targeted ADC can enable comparable levels of gene-therapy cell engraftment to multi-dose busulfan while avoiding many of busulfan’s common toxicities," said Dr. John Tisdale, Chief of Cellular and Molecular Therapeutics, NHLBI, NIH. "If successfully translated to the clinic, a single dose of a CD117-targeted ADC may improve the risk/benefit profile for patients with hemoglobinopathies who are considering HSC gene-therapy."

Allogeneic HSC Transplant. In support of using a CD117-targeted conditioning ADC in allogeneic HSC transplant, Magenta presented a poster demonstrating successful use of a tool CD117-ADC in combination with lymphodepleting antibodies that enabled allogeneic transplant in immune-competent murine models. These studies support the therapeutic potential of CD117-targeted ADCs, without the use of toxic chemotherapy, for conditioning in allogeneic HSC transplantation.

Phase 1/2 Clinical Trial. Magenta is on track to open a Phase 1/2 clinical trial this month to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MGTA-117, a CD117-targeted ADC. Preclinical efficacy and GLP toxicology studies with MGTA-117: (i) enabled selection of the starting dose in this dose-escalating Phase 1/2 clinical trial, (ii) demonstrated that MGTA-117 efficiently depleted stem cells, (iii) showed that MGTA-117 was efficiently cleared from the body in the preclinical models which is especially important for autologous gene therapy or allogeneic stem cell transplants, and (iv) showed that MGTA-117 was well-tolerated. MGTA-117, as a targeted conditioning therapy, is designed to substantially improve against the known safety and tolerability concerns of current non-specific conditioning agents which include busulfan, other chemotherapies, and irradiation. Magenta expects to provide the details of the MGTA-117 clinical trial design at its company presentation at the 2022 JP Morgan Healthcare Conference on January 13, 2022.