Monthly Archives: January 2022

Cell Biology

Magenta Therapeutics Highlights Recent Pipeline Progress and Milestone Expectations for 2022 – BioSpace

-- MGTA-117 Phase 1/2 clinical trial is open for enrollment for patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes; clinical data expected in 2022 -

-- CD45 antibody drug conjugate is Magentas second conditioning program; dose range toxicology results expected in second half of 2022 --

-- MGTA-145 stem cell mobilization program focused on dose and administration optimization and sickle cell disease clinical trial with initial data expected in second half of 2022 -

-- Focused program spending allows for extended cash runway; ended 2021 with approximately $162 million in cash reserves with expectation to fund operating plan into Q4 2023 --

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Magenta Therapeutics (NASDAQ: MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplant to more patients, today highlighted progress across its portfolio of targeted conditioning and stem cell mobilization programs and set out its milestone expectations for both clinical and preclinical data in 2022. These updates will also be discussed during a webcast presentation at the 40th Annual J.P. Morgan Healthcare Conference on Thursday, January 13 at 9:45 a.m. EST.

2022 will be an important year for the Magenta portfolio said Jason Gardner, D. Phil., President and Chief Executive Officer, Magenta Therapeutics. We believe we will clinically demonstrate that MGTA-117 targets and binds selectively to CD117-expressing cells, potently depletes those cells and the product profile will be well-tolerated in our Phase 1/2 clinical study. We have developed biomarker assays that we believe will provide early insights into the biologic activity of MGTA-117. We are also thrilled to introduce our second targeted conditioning program in the development pipeline, an antibody drug conjugate targeting CD45 which has the potential to deplete both stem cells and immune cells without chemotherapy. Finally, with our MGTA-145 program, we are focused on optimizing the collection yield of mobilized stem cells. We believe MGTA-145 can offer a faster and more reliable mobilization regimen for stem cell transplantation as well as ex vivo and in vivo gene therapies.

Targeted Conditioning

MGTA-117 Program:

2022 Clinical Data from Phase 1/2 Clinical Trial: Evaluating Target Selectivity, Potency and Tolerability. The MGTA-117 Phase 1/2 clinical trial is open for enrollment. This dose escalation clinical trial will evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of MGTA-117 as a single dose in patients with relapsed/refractory Acute Myeloid Leukemia (AML) and Myelodysplasia-Excess Blasts (MDS-EB).

Specifically, dosing cohorts expected to enroll in 2022 will allow for evaluation of MGTA-117s ability to:

Magentas preclinical evidence supports the MGTA-117 target selectivity, potency and tolerability profile. In GLP toxicology studies, MGTA-117 potently depleted stem cells at a dose level where there were no drug-related findings in hepatic, reproductive, neurologic, cardiovascular, or respiratory organs.

Phase 1/2 Clinical Trial Design for MGTA-117. MGTA-117 will be assessed in patients with relapsed/refractory AML and MDS-EB in a multi-center, open-label, single-ascending-dose trial. Patients in the first cohort will receive 0.02 mg/kg administered intravenously (IV), and subsequent cohort doses will be determined in accordance with a modified Fibonacci sequence.

Magenta will assess data from each cohort and, after collection of adequate safety, pharmacokinetic and pharmacodynamic data, Magenta intends to engage with the U.S. Food and Drug Administration (FDA) to transition to the primary target population of patients eligible for stem cell transplantation. In addition, Magenta plans to explore MGTA-117 as a targeted conditioning agent for stem cell gene therapies.

CD45-Antibody Drug Conjugate Program:

Magenta has initiated investigational new drug application-enabling studies on its second targeted conditioning program, an antibody drug conjugate (ADC) targeting CD45. Due to the expression of CD45 on stem cells and immune cells, Magentas CD45-ADC is designed to selectively target and deplete stem cells and lymphocytes, which could allow patients with blood cancers and autoimmune diseases to avoid use of chemotherapy prior to stem cell transplant. Magenta expects to have preclinical data from a dose ranging toxicology study in the second half of 2022.

Stem Cell Mobilization and Collection

MGTA-145 Dosing and Administration Optimization Clinical Trial. As previously disclosed, Magenta intends to initiate a dosing and administration optimization clinical trial with MGTA-145 in combination with plerixafor. Clinical data from a Phase 2 investigator-initiated clinical trial with 25 multiple myeloma patients showed that MGTA-145, in combination with plerixafor, mobilized a sufficient number of stem cells for transplantation in 88% of patients (22/25). In addition, all patients transplanted with cells mobilized by MGTA-145 plus plerixafor as of the data cut-off date had successful engraftment (18/18 patients) with prolonged durability through the 100-day follow-up period (13/13 patients). The regimen was generally well-tolerated. Magenta believes there are specific opportunities to further improve cell collection yield by adjustments to the regimen dosing, and administration timing. Magenta expects to generate data from this healthy subjects clinical trial in the second half of 2022.

Sickle Cell Disease (SCD) Stem Cell Mobilization Phase 2 Clinical Trial. Magenta is advancing trial initiation activities. The trial is designed to evaluate mobilization and collection of stem cells in adults and adolescents with SCD. Magenta and its clinical collaboration partner, bluebird bio, will each characterize the collected cells. Magenta plans to gene-modify the cells and transplant them into established preclinical models to evaluate graft quality and engraftment. Data from this clinical trial could provide proof-of-concept for MGTA-145, in combination with plerixafor, as a first-line mobilization regimen for patients with SCD and, more broadly, across other gene therapy applications. Magenta expects to generate data from this clinical trial in the second half of 2022.

Cash Guidance

With focused allocation of capital and resources on both clinical stage programs and CD45-ADC, Magenta now expects its cash reserves to fund its operating plan into the fourth quarter of 2023. Magenta ended 2021 with approximately $162 million of cash, cash equivalents, and marketable securities (unaudited).

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines designed to bring the curative power of stem cell transplant to more patients with blood cancer, genetic diseases and autoimmune diseases. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise to revolutionize immune and blood reset to allow more patients to take advantage of the curative potential of stem cell transplant as well as potentially improve eligibility for future gene therapies.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statements

This press release may contain forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws, including express or implied statements regarding Magentas future expectations, plans and prospects, including, without limitation, statements regarding expectations, plans and timing for preclinical activities, clinical trials and related results, the development of product candidates and advancement of preclinical and clinical programs, the potential benefits and expected performance of product candidates, projections regarding long-term growth, cash, cash equivalents and marketable securities, as well as other statements containing words such as anticipate, believe, continue, could, designed, endeavor, estimate, expect, intend, may, might, plan, potential, predict, project, seek, should, target, will or would and similar expressions that constitute forward-looking statements under the Private Securities Litigation Reform Act of 1995. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation: uncertainties inherent in preclinical and clinical studies and in the availability and timing of data from ongoing and planned clinical and preclinical studies; the ability to initiate, enroll, conduct or complete ongoing and planned preclinical and clinical studies; whether results from preclinical or earlier clinical studies will be predictive of the results of future studies; discussions with governmental agencies such as the FDA; the expected timing of submissions for regulatory approval to conduct or continue trials or to market products; whether Magenta's cash resources will be sufficient to fund Magenta's foreseeable and unforeseeable operating expenses and capital expenditure requirements; risks, uncertainties and assumptions regarding the impact of the continuing COVID-19 pandemic on Magentas business, operations, strategy, goals and anticipated timelines, and other risks concerning Magenta's programs and operations are described in additional detail in its Annual Report on Form 10-K filed on March 3, 2021, as updated by Magentas most recent Quarterly Report on Form 10-Q, and its other filings made with the Securities and Exchange Commission from time to time. Although Magenta's forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known by Magenta. As a result, you are cautioned not to rely on these forward-looking statements. Any forward-looking statement made in this press release speaks only as of the date on which it is made. Magenta undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future developments or otherwise.

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Magenta Therapeutics Highlights Recent Pipeline Progress and Milestone Expectations for 2022 - BioSpace

Cell Biology

Crew Starts Week with Space Agriculture, Human Cells and Spacesuits – NASA

Pictured from left, are the Soyuz MS-19 crew ship and the Nauka multipurpose laboratory module with the Prichal docking module attached.

The Expedition 66 crew kicked off Monday promoting space agriculture and observing how the human cell adapts to weightlessness. Two cosmonauts are also gearing up for the first spacewalk of 2022 set to begin next week at the International Space Station.

Growing plants in space is critical to keeping crews healthy as NASA and its international partners plan human missions to the Moon, Mars and beyond. Just like humans living in space, microgravity affects plants and scientists want to learn how to successfully grow crops in space to sustain crews with less support from Earth.

Today, NASA Flight Engineer Mark Vande Hei harvested the shoots and roots of Arabidopsis plants grown on petri plates inside the Veggie facility. Fellow NASA Flight Engineer Raja Chari collected the harvested samples and stowed them in a science freezer for later analysis. The APEX-07, or Advanced Plant Experiment-07, study is looking at how microgravity affects genetic expression in plants.

ESA (European Space Agency) astronaut Matthias Maurer worked throughout Monday on the Cytoskeleton space biology study. That study takes place in the Kibo laboratory module and uses the Life Science Glovebox to explore how the internal machinery of the human cell is impacted by long-term space missions.

NASA Flight Engineer Kayla Barron also worked in Kibo and set up the new Mochii electron-scanning microscope to identify trace particles aboard the station. NASA astronaut Thomas Marshburn fed mice and cleaned their habitats throughout Monday before inspecting and cleaning hatch seals in the stations U.S. segment.

Commander Anton Shkaplerov and Flight Engineer Pyotr Dubrov partnered together during the morning on a pair of Russian studies looking at how space affects heart activity and arm muscles. The duo later spent the rest of the day setting up Russian Orlan spacesuits for a spacewalk set to begin on Jan. 19. The two cosmonauts will spend about seven hours in the vacuum of space outfitting the stations newest modules, Nauka and Prichal.

Learn more about station activities by following thespace station blog,@space_stationand@ISS_Researchon Twitter, as well as theISS FacebookandISS Instagramaccounts.

Get weekly video highlights at:http://jscfeatures.jsc.nasa.gov/videoupdate/

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Crew Starts Week with Space Agriculture, Human Cells and Spacesuits - NASA

Cell Biology

Study uncovers how cancers resist targeted treatment – The Institute of Cancer Research, London – The Institute of Cancer Research

Scientists have revealed how cancer can resist PARP inhibitors, a precision medicine used to treat thousands of patients worldwide.

Their study found that some cancer cells could dodge the effects of PARP inhibitors, by removing the PARP proteins that get trapped onto their DNA.

The researchers believe that existing drugs including a medicine used to treat alcohol addiction could potentially be used to make PARP inhibitors more effective by preventing the cancer cells from removing PARP.

In the future, the findings could also help predict what patients are more likely to respond to PARP inhibitors.

The study, led by scientists at The Institute of Cancer Research, London, is published in Nature Cell Biology andwas funded by Cancer Research UK, with additional support from Breast Cancer Now.

PARP inhibitors, which include olaparib and rucaparib, are used to treat some patients with ovarian, breast, prostate and pancreatic cancers usually patients who have inherited a faulty BRCA1 or BRCA2 gene.

So far, more than 30,000 patients have been treated with olaparib worldwide.

PARP inhibitors target PARP1, one of the DNA repair tools rendering it inactive and locking it in place, trapped on the DNA. Not only does this stop DNA repair, but the trapping of PARP1 onto DNA will eventually cause cancer cells to die. But PARP inhibitors dont work for everyone, and its estimated that over 40 per cent of patients with a faulty BRCA1 or BRCA2 gene dont respond to them.

To understand this better, Professor Chris Lord and his team at The Institute of Cancer Research (ICR) used cell lines and protein analysis techniques find out how cancer cells become resistant.

They looked for proteins that attached to PARP1 only when it was trapped, and that might play a role in detaching it from DNA. The team found that a small molecule called p97 could play a crucial role in prizing PARP1 from the DNA, saving cancer cells from destruction.

The researchers wanted to see what happened if this last stage was blocked. They used a human organoid, a mini tumour built with tissue from patients with triple negative breast cancer and a BRCA1 mutation; someone who might have qualified for PARP inhibitor treatment.

Blocking p97 made the cancer cells much more vulnerable to the PARP inhibitor talazoparib, suggesting a potential route to tackle treatment resistance. For instance, a 1nM dose of talazoparib killed about 30 per cent of the cancerous organoid, but that went up to 90 per cent when coupled with a p97 inhibitor called disulfiram. This finding suggests that disulfiram, a drug commonly used to treat people with alcohol addiction, could be combined with PARP inhibitors to improve the chances of successful treatment.

For Professor Lord and his team, the next challenge is to translate their new understanding of PARP inhibitor resistance into a way to predict which patients should be treated with PARP inhibitors, and who would be better off getting a different cancer treatment.

Professor Chris Lord, Professor of Cancer Genomicsat The Institute of Cancer Research, London, said:

PARP inhibitors are one of the most exciting classes of precision medicine in cancer treatment today, but we are only now gaining a fuller understanding of why they work in some patients but not in others.

Now that we have uncovered p97s role in controlling PARP inhibitor resistance, we could, in future offer treatments that could save many more lives.

We believe our findings will help us predict which patients should get a PARP inhibitor, which patients might need to combine a PARP inhibitor with other drugs to stand the best chance of successful treatment, or which patients might be better off on a different treatment altogether.

Michelle Mitchell, chief executive of Cancer Research UK, said:

Our scientists helped to discover the BRCA gene over 25 years ago. Now we have drugs that target this mutation, which have saved many lives.

But we know that cancer can quickly outwit even the best treatments. Its important to understand the mechanisms behind resistance so that we can make the drugs we already have work better and for more people.

Using new combinations of drugs that are already available is a smart way to get one step ahead of cancer, and we will need more research to know how effective this approach might be for PARP inhibitors. But the findings from this study are a promising new way to stack the odds in the patients favour, by offering treatment which works best for them.

Dr Simon Vincent, Director of Research, Support and Influencing at Breast Cancer Now, said:

People who have inherited an altered gene will have a higher risk of developing breast cancer and every year thousands of people in the UK with an altered BRCA1 or BRCA2 gene are diagnosed with the disease.

PARP inhibitor drugs work well against cancer cells with an altered BRCA gene, however, they dont work for everyone and some cancers become resistant to this targeted treatment, making it important we continue to fund research into understanding drug resistance. Excitingly, this research suggests that a medicine currently used to treat alcohol addiction could be used in combination with PARP inhibitors to make treatment for breast cancer, caused by an altered BRCA gene, more effective. We hope this research will lead to new treatment options and better ways to tailor therapy to each individual patient, so that everyone can receive treatment that works best for them.

This breakthrough is testament to the tireless efforts of world-class researchers - including many Breast Cancer Now funded UK researchers who, over the last 20 years, have helped develop PARP inhibitor drugs and laid the foundations for this promising discovery.

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Study uncovers how cancers resist targeted treatment - The Institute of Cancer Research, London - The Institute of Cancer Research

Cell Biology

BTIG Initiates Coverage of Ginkgo Bioworks With Buy Rating – GenomeWeb

NEW YORK Investment bank BTIG on Friday initiated coverage of synthetic biology company Ginkgo Bioworks with a Buy rating and a price target of $12 on its shares.

BTIG believes that Ginkgo's cell programming platform will enable less expensive and more sustainable nucleic acid vaccines, antibiotics, and cell and gene therapies. Beyond pharma, BTIG expects Ginkgo to be able to increase global food availability and crop yields, help grow fermented cannabis, and produce materials and chemicals more sustainably.

Ginkgo's revenues come from usage fees for its Foundry lab and from royalties paid on sales of its customers' products, milestones, or equity stakes used to capture downstream value.

Foundry is a biology lab with custom software, robotic automation, data science, and analytics. In addition to Foundry, Ginkgo maintains a proprietary genetic database called Codebase, which contains 440 million proprietary gene sequences and over 3.4 billion unique gene sequences pulled from public databases.

BTIG estimates that by spreading its services across diverse industries, Ginkgo will have access to a total addressable market for bioengineered products that global consultancy McKinsey expects to grow to $2 trillion-$4 trillion annually by 2040.

Ginkgo currently runs over 70 major cell programs, including a novel antibiotic discovery cell program with Roche, a cell-based nitrogen fertilizers production program with Bayer Crop Science, a cannabinoid production partnership with Cronos Group, and an animal-free protein food products cell program with Motif FoodWorks.

Ginkgo was founded by five MIT scientists including Tom Knight in 2009, following Knight's earlier work on BioBricks, a standardized way to combine interchangeable segments of DNA.

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BTIG Initiates Coverage of Ginkgo Bioworks With Buy Rating - GenomeWeb