Monthly Archives: June 2022

TUEBINGEN, Germany and HOUSTON and CAMBRIDGE, Mass., June 07, 2022 (GLOBE NEWSWIRE) -- Immatics N.V. (Nasdaq: IMTX, Immatics), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, and Editas Medicine, Inc. (Nasdaq: EDIT, Editas Medicine), a leading genome editing company, today announced that the two companies have entered into a strategic research collaboration and licensing agreement to combine gamma-delta T cell adoptive cell therapies and gene editing to develop medicines for the treatment of cancer. As part of the licensing agreement, Immatics gains non-exclusive rights to Editas Medicines CRISPR technology and intellectual property. Editas Medicine is the exclusive licensee of Harvard and Broad Institutes Cas9 patent estates and Broad Institutes Cas12a patent estate for human medicines.

By combining Editas Medicines gene editing technology with Immatics ACTallo allogeneic, off-the-shelf adoptive cell therapy platform based on gamma-delta T cells, gamma-delta T cells can be redirected to cancer cell targets with the goal of creating cells with enhanced tumor recognition and destruction.

Engineered cell therapies have the potential to significantly impact the treatment paradigm for cancer, and our partnership with the esteemed team at Editas Medicine will provide us with further versatility and flexibility in how we engineer our ACTallo cell therapies based on a specific tumor target, said Rainer Kramer, Ph.D., Chief Business Officer, Immatics. It has always been our focus to deliver innovative science to cancer patients and this collaboration with Editas Medicine will enable us to access CRISPR technologies and apply them to our off-the-shelf gamma-delta T cell platform.

We believe that our gene editing technology can modulate and enhance the potential of cell therapies to deliver transformative medicines for the treatment of cancer. We are excited to work with the team at Immatics to develop new experimental medicines with enhanced tumor fighting abilities to help patients with cancer, said Gilmore ONeill, M.B., M.M.Sc., President and Chief Executive Officer, Editas Medicine.

Under the terms of the agreement, Editas Medicine will be eligible to receive an undisclosed upfront cash payment as well as additional milestone payments based on development, regulatory, and commercial milestones. In addition, Immatics will pay royalties on future net sales on any products that may result from this collaboration.

About ImmaticsImmatics combines the discovery of true targets for cancer immunotherapies with the development of the right T cell receptors with the goal of enabling a robust and specific T cell response against these targets. This deep know-how is the foundation for our pipeline of Adoptive Cell Therapies and TCR Bispecifics as well as our partnerships with global leaders in the pharmaceutical industry. We are committed to delivering the power of T cells and to unlocking new avenues for patients in their fight against cancer.

For regular updates about Immatics, visit http://www.immatics.com. You can also follow us on Instagram, Twitter and LinkedIn.

About Editas MedicineAs a leading genome editing company, Editas Medicine is focused on translating the power and potential of the CRISPR/Cas9 and CRISPR/Cas12a genome editing systems into a robust pipeline of treatments for people living with serious diseases around the world. Editas Medicine aims to discover, develop, manufacture, and commercialize transformative, durable, precision genomic medicines for a broad class of diseases. Editas Medicine is the exclusive licensee of Harvard and Broad Institutes Cas9 patent estates and Broad Institutes Cas12a patent estate for human medicines. For the latest information and scientific presentations, please visit http://www.editasmedicine.com.

Immatics Forward-Looking StatementsCertain statements in this press release may be considered forward-looking statements. Forward-looking statements generally relate to future events or Immatics future financial or operating performance. For example, statements concerning the timing of product candidates and Immatics focus on partnerships to advance its strategy are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as may, should, expect, intend, will, estimate, anticipate, believe, predict, potential or continue, or the negatives of these terms or variations of them or similar terminology. Such forward-looking statements are subject to risks, uncertainties, and other factors which could cause actual results to differ materially from those expressed or implied by such forward looking statements. These forward-looking statements are based upon estimates and assumptions that, while considered reasonable by Immatics and its management, are inherently uncertain. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Factors that may cause actual results to differ materially from current expectations include, but are not limited to, various factors beyond management's control including general economic conditions and other risks, uncertainties and factors set forth in filings with the SEC. Nothing in this press release should be regarded as a representation by any person that the forward-looking statements set forth herein will be achieved or that any of the contemplated results of such forward-looking statements will be achieved. You should not place undue reliance on forward-looking statements, which speak only as of the date they are made. Immatics undertakes no duty to update these forward-looking statements.

Editas Medicine Forward-Looking Statements This press release contains forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, target, should, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include statements regarding the expected benefits of Editas Medicines collaboration with Immatics, including any future payments it may receive under the strategic research collaboration and licensing agreement and the potential to generate medicines from the collaboration. Editas Medicine may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of pre-clinical studies and clinical trials and clinical development of Editas Medicines product candidates; availability and timing of results from pre-clinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products and availability of funding sufficient for Editas Medicines foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption Risk Factors included in Editas Medicines most recent Annual Report on Form 10-K, which is on file with the Securities and Exchange Commission, as updated by Editas Medicines subsequent filings with the Securities and Exchange Commission, and in other filings that Editas Medicine may make with the Securities and Exchange Commission in the future. Any forward-looking statements contained in this press release represent Editas Medicines views only as of the date hereof and should not be relied upon as representing its views as of any subsequent date. Except as required by law, Editas Medicine explicitly disclaims any obligation to update any forward-looking statements.

Source: Editas Medicine, Inc.

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Immatics and Editas Medicine Enter Strategic Research Collaboration and Licensing Agreement to Combine Gamma-Delta T Cell Adoptive Cell Therapies and...

For years, the American Society of Clinical Oncologys annual meeting has served as the main forum for advances in cancer immunotherapies like Merck & Co.s Keytruda and Bristol Myers Squibbs Opdivo.

While new data continue to emerge for those drugs and their competitors, this years conference was headlined by dramatic data for another type of cancer medicine from AstraZeneca and Daiichi Sankyo, which put pressure on rival Gilead. And with CAR-T therapies now established, attention has shifted to other emerging approaches for training the immune system to attack tumors.

Read on for updates on Gilead, bispecific antibodies for blood cancer and gamma delta cell therapy.

ASCO is an important conference for any biotech developing a cancer drug. But this years meeting was particularly so for Gilead, which has spent a decade and billions of dollars trying to build its oncology business. Analysts and investors were eagerly awaiting the details of a key study of the breast cancer drug Trodelvy, for which it paid $21 billion to acquire last year. Updates were also expected for magrolimab, another cancer medicine Gilead recently bought in a large deal.

The drugs either underwhelmed or were upstaged by others, however. Trodelvy led to a 1.5-month improvement over chemotherapy on a measure of tumor progression in a late-stage study of patients with a common form of metastatic breast cancer. The result fell short of the 2-month target doctors surveyed by analyst firm RBC Capital Markets felt would warrant meaningful use, according to a research note.

Trodelvy was also overshadowed by AstraZeneca and Daiichi Sankyos rival breast cancer drug, Enhertu, whose data in so-called HER2 low tumors were so striking they received a standing ovation at the meeting.

All the enthusiasm for Trodelvy has evaporated after those results, wrote Baird analyst Brian Skorney in a note on Sunday, adding that Enhertus likely approval in HER2 low breast cancer could limit Trodelvys revenue potential.

Analysts were similarly unimpressed by the latest data for magrolimab, a blood cancer drug that was slowed by safety concerns this year. Initial data showed a response rate of 50% for a combination of magrolimab and the chemotherapy azacitidine in an early-stage trial in myelodysplastic syndrome. That rate has fallen to 33% with additional data, barely surpassing whats been observed in tests of chemotherapy alone, Skorney wrote.

Complete response rates slipped in a Phase 1 acute myeloid leukemia study as well. The updates show Gileads drug has sufficient activity, though its perhaps not the home run it was initially hoped to be, wrote RBC analyst Brian Abrahams in a note to clients.

Gilead will likely need to show more before investors view the cancer portfolio as a major growth driver, Abrahams added. Shares ticked down 2% in early Monday trading.

The biotech did get a reprieve on Friday, however, announcing that regulators had lifted their last remaining hold on studies of magrolimab in lymphoma and multiple myeloma.

Cell therapy has become a powerful new treatment option for blood cancers like lymphoma and multiple myeloma. Approved drugs from Gilead, Bristol Myers Squibb, Novartis and Johnson & Johnson use souped-up immune cells genetically modified and infused back into patients to attack cancers.

But the approach, while potent, involves a painstaking manufacturing process that requires physicians to carefully time treatment. In multiple myeloma, Bristol Myers and J&J have struggled to keep up with demand, Stat News has reported, further complicating cell therapy's use.

While drugmakers expect to overcome those hurdles with time, they are busy advancing other ways to redirect immune cells to target cancer. One alternative uses an antibody to latch onto protein flags found on the surface of immune cells and their cancerous targets, bringing them into tumor-killing contact.

These so-called bispecific antibodies have already shown promise in some of the same blood cancers addressed by CAR-T cell therapies. At ASCO, Roche and J&J revealed updated clinical trial data supporting their respective medicines for lymphoma and multiple myeloma. AbbVie and partner Genmab, meanwhile, will present data on their lymphoma bispecific antibody at the European Hematology Association's meeting next weekend.

Scott Gottlieb, formerly Food and Drug Administration commissioner and currently a member of Pfizers board, pointed to bispecific antibody data as some of the most exciting to come out of ASCO this year.

"That data looks very promising," he said on CNBCs Squawkbox program Monday, noting the therapies from Roche and partners AbbVie and Genmab specifically.

Specifically, Roche's data showed treatment led to responses in half of patients with relapsed or refractory diffuse large B-cell lymphoma who were treated in the study. Nearly 40% went into remission.

Notably, about a third of the 154 participants had previously received CAR-T therapies, which have recently been approved in the U.S. for earlier use in treating advanced lymphoma.

"We still need longer follow-up for the bispecific antibodies," said Kerry Savage, a medical oncologist at The University of British Columbia, who discussed Roche's abstract at ASCO on Friday. "We don't know the curative potential yet, but it's certainly encouraging so far."

AbbVie and Genmab's results, which will be presented on Saturday at EHA, showed a slightly higher overall response rate of 63% and a similar remission rate of 39% among adults with several variations of relapsed or refractory large B-cell lymphoma.

J&J, meanwhile, brought updated data to ASCO for its multiple myeloma bispecific teclistamab, which were also published in The New England Journal of Medicine. The data showed treatment could beat back cancer and, in about 40% of patients, lead to remission.

"The high rate of deep and durable responses in this population indicates the potential for teclistamab to provide substantial clinical benefit to a broader population of patients," researchers wrote in NEJM.

The search for more convenient alternatives to personalized cell therapies has led to other off-the-shelf strategies besides bispecific antibodies. One emerging approach involves gamma delta T cells, rare white blood cells that can recognize a range of targets.

Adicet Bio, In8Bio, Immatics, among others, are developing treatments and multiple large companies have shown interest in their work. Bristol Myers Squibb just last week expanded an existing deal with Immatics, while Takeda and Johnson & Johnson have recently made investments, too.

Adicets program, a potential treatment for non-Hodgkins lymphoma, is the most advanced of the group, making its trial results an important proof point for the field.

Prior to the meeting, Adicet said four of six treated patients with a low or medium dose went into remission, with two of the three patients treated still cancer free after three months. Importantly, there were no serious immune or neurological side effects reported.

At ASCO, Adicet disclosed results from two additional patients as well as longer follow-up from others. While early, the findings are in the range with CAR-T therapy. As of May 31, six of eight patients including two at the highest tested dose had responded to treatment. All six initially went into remission.

Notably, these were heavily pretreated patients, three of whom whose disease had progressed after CAR-T. Adicet hasnt reported any cases of severe cytokine release syndrome, a common side effect of CAR-T.

Yet the treatments durability remains in question. Though four of the complete responses are ongoing, only one has lasted longer than six months. One patient previously in remission died from COVID-19, while another relapsed.

Adicet plans to pick a dose to advance into further testing. The company amended its trial to include a higher dose as well as potentially evaluate a multiple-dose regimen, a strategy other off-the-shelf cell therapy developers are testing as well.

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ASCO 2022: Gilead's tough weekend, bispecific progress and 'gamma delta' cell therapy - BioPharma Dive

An acceptable safety profile and durable complete response (CR), partial response (PR) rates were observed with the chimeric antigen receptor (CAR) T-cell therapy CTX130 in the phase 1 COBALT-LYM study of patients with relapsed/refractory T-cell lymphomas, said Swaminathan P. Iyer, MD, professor of medicine in the Department of Lymphoma and Myeloma at the University of Texas MD Anderson Cancer Center.

Iyer served as lead author of a study presented today at the 2022 European Hematology Association (EHA) Congress, titled, "The COBALT-LYM Study of CTX130: A Phase 1 Dose Escalation Study of CD70-Targeted Allogeneic CRISPR-Cas9Engineered CAR-T Cells in Patients with Relapsed/Refractory (R/R) T-cell Malignancies.

Transcript

What is the mechanism of action for CTX130 in T-cell lymphoma, and can you discuss how the COBALT-LYM study was conducted?

So, CTX130 is a first-in-class allogeneic CAR T-cell for T-cell lymphomas. And the study that put together this CAR T was called the COBALT-LYM study, and the target here is CD70, [which] is a protein that is expressed on the surface of cells. It's been found that 85% of T-cell lymphomas express them.

A lot of investigations of the past have been done on CD70 in terms of antibodies and antibody drug conjugates. What's different about this construct, it's an allogeneic CAR T, which means healthy donors are selected and the chimeric antigen receptor is created using CD70 as a construct, and using the other activation and costimulatory domains.

This is the product, CTX130, and this a phase 1 dose-finding study allowable in patients who express at least greater than 10% of CD70 in patients with PTCL [peripheral t-cell lymphoma] and patients with CTCL [transformed cutaneous t-cell lymphoma]. For PTCL, the prior criteria is one prior line of therapy, for CTCL its at least 2 systemic therapies.

The patients were enrolled, and you will see the presentation this afternoon, from the abstract, it's 18 patients data who participated in this study, and 70% overall response rate and 29% CR based on the abstract. So, this is the CTX130, and there's more data that will be presented this afternoon.

Can you discuss efficacy and safety findings reported at EHA2022 of the COBALT-LYM study?

So, the first thing is safety. Since it's a dose-finding study, phase 1, the main goal of part A, which is the dose escalation, is safety. Since it's a CAR T construct, it has certain potential side effects that are very different from other drugs, if you will.

So, the things that you would expect in CAR Ts are cytokine release syndrome [CRS], the neurological toxicity called ICANS [immune effector cell-associated neurotoxicity syndrome], and since its an allogeneic CAR T, GVHD [graft versus host disease], and since it's an effective therapy, tumor lysis syndrome (TLS), and then everything else that other drugs might cause.

So, in this particular study, the safety was acceptable across all those levels4 of those levels tested, 1, 2, 3, and 4, going from 30 to 900 million cells, and the safety was acceptable. The CRS was mostly grade 1 and 2, the neurological toxicity was grade 1 and 2, all of which resolved. There was no TLS, no GVHD.

There were some infections seen. One out of the 4 infections of the grade 3 or higher were attributable to the CAR T, but otherwise, there are other treatment-emergent SAEs [serious adverse events], such as syncope, presyncope, tumor hemorrhagethey were all not deemed related to CTX130. So, safety wise, very acceptable.

Efficacy, I just mentioned 70% overall response rate with 29% CRs. And some of these CRs were durable CRs. You will see that many of them could be bridged to the more longer-term consolidation therapy. But for the first time you're seeing responses in T-cell lymphomas, patients who did not achieve prior responses like a CR, and now we're getting to the point where you have PRs and CRs that are lasting.

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Dr Swaminathan P. Iyer on Efficacy, Safety of CD70-Targeted CAR T-Cell Therapy in R/R T-Cell Lymphoma - AJMC.com Managed Markets Network

DUBLIN--(BUSINESS WIRE)--The "Single Cell Sequencing Market Research Report by Product (Consumables and Instruments), Application, End-User, Region (Americas, Asia-Pacific, and Europe, Middle East & Africa) - Global Forecast to 2027 - Cumulative Impact of COVID-19" report has been added to ResearchAndMarkets.com's offering.

The Global Single Cell Sequencing Market size was estimated at USD 2,301.59 million in 2021, USD 2,407.37 million in 2022, and is projected to grow at a Compound Annual Growth Rate (CAGR) of 4.77% to reach USD 3,044.54 million by 2027.

Competitive Strategic Window:

The Competitive Strategic Window analyses the competitive landscape in terms of markets, applications, and geographies to help the vendor define an alignment or fit between their capabilities and opportunities for future growth prospects. It describes the optimal or favorable fit for the vendors to adopt successive merger and acquisition strategies, geography expansion, research & development, and new product introduction strategies to execute further business expansion and growth during a forecast period.

FPNV Positioning Matrix:

The FPNV Positioning Matrix evaluates and categorizes the vendors in the Single Cell Sequencing Market based on Business Strategy (Business Growth, Industry Coverage, Financial Viability, and Channel Support) and Product Satisfaction (Value for Money, Ease of Use, Product Features, and Customer Support) that aids businesses in better decision making and understanding the competitive landscape.

Market Share Analysis:

The Market Share Analysis offers the analysis of vendors considering their contribution to the overall market. It provides the idea of its revenue generation into the overall market compared to other vendors in the space. It provides insights into how vendors are performing in terms of revenue generation and customer base compared to others. Knowing market share offers an idea of the size and competitiveness of the vendors for the base year. It reveals the market characteristics in terms of accumulation, fragmentation, dominance, and amalgamation traits.

The report provides insights on the following pointers:

1. Market Penetration: Provides comprehensive information on the market offered by the key players

2. Market Development: Provides in-depth information about lucrative emerging markets and analyze penetration across mature segments of the markets

3. Market Diversification: Provides detailed information about new product launches, untapped geographies, recent developments, and investments

4. Competitive Assessment & Intelligence: Provides an exhaustive assessment of market shares, strategies, products, certification, regulatory approvals, patent landscape, and manufacturing capabilities of the leading players

5. Product Development & Innovation: Provides intelligent insights on future technologies, R&D activities, and breakthrough product developments

The report answers questions such as:

1. What is the market size and forecast of the Global Single Cell Sequencing Market?

2. What are the inhibiting factors and impact of COVID-19 shaping the Global Single Cell Sequencing Market during the forecast period?

3. Which are the products/segments/applications/areas to invest in over the forecast period in the Global Single Cell Sequencing Market?

4. What is the competitive strategic window for opportunities in the Global Single Cell Sequencing Market?

5. What are the technology trends and regulatory frameworks in the Global Single Cell Sequencing Market?

6. What is the market share of the leading vendors in the Global Single Cell Sequencing Market?

7. What modes and strategic moves are considered suitable for entering the Global Single Cell Sequencing Market?

Market Dynamics

Drivers

Restraints

Opportunities

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Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/nel4wa

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Insights on the Single Cell Sequencing Global Market to 2027 - Ongoing Demand for Personalized or Customized Medicine Presents Opportunities -...

More than a dozen rectal cancer patients in the United States have seen their cancer disappear after undergoing experimental immunotherapy, in what doctors are calling an astonishing result.

The patients, who were part of a small clinical trial led by researchers from New Yorks Memorial Sloan Kettering (MSK) Cancer Center, saw their tumours vanish after being treated with an experimental drug called dostarlimab.

Details of the trial were published on Sunday in the New England Journal of Medicine.

The paper described the results of 12 patients with rectal cancer, all of whom saw their cancer vanish after treatment with dostarlimab.

Participants received a dose of dostarlimab every three weeks for six months, with the idea being that they would need to undergo standard treatments of chemotherapy, radiation therapy and surgery following treatment.

However, researchers found that in every case, the cancer was cleared through the experimental treatment alone.

The trial has been hailed as a first in cancer treatment, with one of the papers authors, Dr Luis Diaz Jr of Memorial Sloan Kettering, telling the New York Times that he knew of no other study in which a treatment completely obliterated a cancer in every patient.

I believe this is the first time this has happened in the history of cancer, he said.

Immunotherapy harnesses the bodys own immune system to identify and destroy cancer cells.

The trial focussed on a subset of rectal cancer patients whose cancer had a specific mutation, MSK said in a statement.

This sort of rectal cancer, known as "mismatch repair-deficient" (MMRd) rectal cancer, tends to respond poorly to standard chemotherapy regimens. In the trial, researchers wanted to investigate if immunotherapy alone could beat rectal cancer that had not spread to other tissues, the organisation said.

The research, which is ongoing, has seen at least 14 patients and counting have their tumours disappear, with none of them experiencing significant side effects, it added.

There was no need for standard treatments of radiation, surgery, or chemotherapy, and the cancer has not returned in any of the patients, who have been cancer-free for up to two years, it said.

Its incredibly rewarding to get these happy tears and happy emails from the patients in this study who finish treatment and realise, Oh my God, I get to keep all my normal body functions that I feared I might lose to radiation or surgery, said Dr Andrea Cercek of Memorial Sloan Kettering, who co-led the trial.

Inspiration for the study came from a previous trial led by Dr Diaz, which saw patients taking a drug called pembrolizumab, the New York Times reported. That trial, which involved patients with advanced cancer that resisted standard treatment, saw participants tumours stabilise, shrink and even vanish.

In the current trial, researchers wanted to see what a similar drug, dostarlimab, would do if used before the cancer cells had a chance to spread.

This sort of treatment focuses on particular proteins called checkpoints, which are made by some types of immune system cells as well as some cancer cells, according to the USNational Cancer Institute. The checkpoints, which keep immune responses from being too strong, can sometimes prevent immune cells from effectively killing cancer cells.

Like pembrolizumab, dostarlimab is a checkpoint inhibitor: It essentially releases the brakes on an immune cell, freeing it to recognise and attack cancer cells, according to MSK.

When the brakes are taken off the immune cells, MMRd cells look especially strange because they have so many mutations. So the immune cells attack with much more force, Dr Cercek said.

The results have provided what may be an early glimpse of a revolutionary treatment shift, Dr Hanna Sanoff, an oncologist at the Lineberger Comprehensive Cancer Center at the University of North Carolina, who was not involved in the trial, wrote in an editorial accompanying the paper.

However, she added that although the results are cause for great optimism, such an approach cannot yet supplant our current curative treatment approach.

Whether the results of this small study conducted at Memorial Sloan Kettering Cancer Center will be generalisable to a broader population of patients with rectal cancer is also not known, she said.

In order to provide more information regarding which patients might benefit from immunotherapy, subsequent trials should aim for heterogeneity in age, coexisting conditions, and tumour bulk.

The clinical trial is continuing to enrol patients and is growing, the MSK researchers said. They are also investigating to see if the same method can beat other cancers, and are looking at patients with gastric (stomach), prostate, and pancreatic cancers.

Excerpt from:
This breakthrough drug trial saw cancer vanish in every patient - Euronews

The longest duration of reduction in red blood cell transfusion dependence was reported among patients with -thalassemia who received continued treatment with luspatercept-aamt in the updated data from the phase 3 BELIEVE trial.

The longest duration of reduction in red blood cell (RBC) transfusion dependence was reported among patients with -thalassemia who received continued treatment with luspatercept-aamt (Reblozyl) in the updated data from the phase 3 BELIEVE trial (NCT02604433), presented at the 2022 EHA Congress.1

Response was assessed as reduction of RBC transfusion burden by at least 33% from baseline and by at least 50% from baseline among patients who received luspatercept vs placebo during any rolling 12- or 24-week interval. With a long-term data cutoff of January 5, 2021, among the 224 patients in the luspatercept arm, 173 patients (77.2%) had at least 33% response during any 12-week interval and 116 (51.8%) had a response during any 24-week interval. A transfusion burden reduction of at least 50% was reported among 112 patients (50%) and 53 patients (23.7%) during any 12- and 24-week interval, respectively.1

These outcomes were compared with prior data cutoff landmarks: May 11, 2018 (primary data cutoff) and January 7, 2019 (intermediate data cutoff). In the primary analysis, 70.5% and 41.1% of patients had at least a 33% reduction in transfusion burden at the 12- and 24-week intervals. These rates were 76.3% and 45.1% in the intermediate analysis, respectively. Reduction of at least 50% were reported at any 12- and 24-week intervals among 40.2% and 16.5% of patients, respectively, in the primary analysis and 44.6% and 20.5% in the intermediate analysis.1

In terms of transfusion independence, at the cutoff of 3 years 12% of patients [who received] luspatercept, achieved transfusion independence, equal to or more than [8] weeks. And that, of course, implies the longest interval of this condition of transfusion in dependence, said Maria Domenica Cappellini, MD, FRCP, FACP, professor of internal medicine at the University of Milan and chief of the Rare Diseases Centre at the Fondazione IRCCS Policlinico Hospital in Italy, during a presentation of the data.

The median longest duration of RBC transfusion independence was 72 days (95% CI, 62-103) with longer-term luspatercept treatment. At the primary and intermediate analysis cutoffs, the rates of RBC transfusion independence lasting at least 8 weeks were 10.7% and 11.2%, respectively, compared with 12.1% in the longer-term analysis.

Continuous treatment with the luspatercept allowed for more patients to experience a reduction in RBC transfusion burden, with longer durations of responses compared [with] the previous cutoff, Cappellini said. We are confident that these [benefits] will be even more clear with longer follow-up and patients with transfusion dependent -thalassemia treated in the BELIEVE study will continue to benefit from luspatercept with over 3 years of treatment.

Additional data showed that the median duration of RBC transfusion burden reduction was 114 days (95% CI, 107-137) and 99 days (95% CI, 95-104) for those with 33% reduction and 50% reduction, respectively, at the long-term analysis cutoff. In the primary data cutoff analysis, the median duration of RBC transfusion burden reduction was 104 days (95% CI, 84-588) for those with at least 33% reduction and 97.5 days (95% CI, 84-588) for those with at least 50% reduction. In the intermediate analysis the median duration was 105 days (95% CI, 84-825) and 99 days (95% CI, 84-825), respectively.

The median treatment duration during the primary, intermediate, and long-term landmark analyses were 64.1 days (95% CI, 3-97), 95.7 days (95% CI, 1.7-128.1), and 153.6 days (95% CI, 1.7-215).

Further, the mean cumulative duration of RBC transfusion burden reduction during any rolling 12-week interval was 627.3 (standard deviation, 390.5) for patients who received luspatercept.1

In terms of RBC transfusion burden change from baseline, Cappellini noted that patients receiving luspatercept required fewer units of blood over time. The mean change in RBC units every 48 weeks from baseline was 4.8 (weeks 1-48), 5.6 (weeks 49-96), 6.2 (weeks 97-144), and 6.4 (weeks 145-192) compared with a 1.1 unit increase reported in weeks 1-48 with placebo.

Cappellini also highlighted that patients achieving an RBC transfusion burden reduction of 50% or higher experienced a greater interval between the transfusions compared with the baseline over time at a mean of +9.9 days (standard deviation, 22.0).1

Luspatercept, an erthyroid maturation agent, is approved for the treatment of anemia in patients with -thalassemia who require regular red blood cell (RBC) transfusions. Additionally, it received an indication for patients who require 2 or more RBC units over 8 weeks for patients with very low- to intermediate-risk myelodysplastic syndromes (MDS) with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.2

BELIEVE was a randomized, double-blind, study comparing luspatercept with placebo.1,3 Investigators enrolled adults with -thalassemia who required regular transfusions of 6 to 20 RBC units in the 24 weeks prior to random assignment, with no transfusion-free period (35 days). Patients were randomly assigned 2:1 to luspatercept (n = 224) plus best supportive care or placebo plus best supportive care (n = 112). Luspatercept was administered subcutaneously 1.0 mg/kg (up to a maximum dose of 1.25 mg/kg) every 3 weeks. Best supportive care included RBC transfusions to maintain baseline hemoglobin levels and iron chelation therapy.1,3

The primary end point was reduction of RBC transfusion burden by at least 33% from baseline with a reduction of at least 2 units in weeks 13 to 24 compared with the 12 weeks prior to randomization.3

Baseline characteristics between the experimental and control arm were well balanced. The median age was 30 years (range, 18-66). Median hemoglobin levels at 24 weeks were 9.31 g/dL (range, 4.5-11.4) and 9.15 g/dL (range, 5.8-11.7) in the luspatercept arm and placebo arm, respectively. The median RBC transfusion burden was 6.12 units (range, 3-14) every 12 weeks in the luspatercept arm and 6.27 (range, 3-12) in the placebo arm. The median burden every 24 weeks was 14 units (range, 6-24) and 15 (range, 6-26), respectively. Further, over half of patients (57.6% and 58.0%, respectively) had a splenectomy.

In terms of liver iron concentration (LIC), at baseline the median LIC in the luspatercept arm was 6.4 mg/g dry weight (range, 0.8-125.0) and 5.05 mg/g dry weight (range, 0.2-53.2) in the placebo arm. An analysis of LIC is ongoing, according to Cappellini.

At data cutoff 127 patients (56.7%) remained on study treatment and 2.7% (n = 6) have completed 192 weeks of treatment. Of the 224 patients in the luspatercept arm, 96 (42.9%) discontinued treatment. The most common reasons for discontinuation were physician decision (23.7%), adverse event (10.3%), or other (5.4%).

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Long-term Treatment With Luspatercept Reduces Transfusion Dependence Associated With -Thalassemia - OncLive

BOSTON--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that five scientific abstracts on the companys portfolio of cystic fibrosis (CF) medicines will be presented at the European Cystic Fibrosis Society's (ECFS) 45th European Cystic Fibrosis Conference held June 8-11, 2022, in Rotterdam, the Netherlands.

Vertex will present the first analysis of data collected in the U.S. CF Foundation Patient Registry (CFFPR) of over 16,000 people with CF treated with TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) for an average of nine months. This first interim analysis of an ongoing five-year post-authorization study (abstract WS22.05) showed that real-world treatment with TRIKAFTA was associated with improved lung function and a 77% reduced risk of pulmonary exacerbations compared to pre-TRIKAFTA baseline, as well as an 87% lower risk of lung transplant and a 74% lower risk of death, compared to the historical 2019 U.S. CFFPR population. No new safety concerns were identified.

Vertex will also present data comparing the annual rate of lung function change in people with CF ages 12 years and older with two F508del mutations (F/F) or one F508del mutation and one minimal function mutation (F/MF) treated with TRIKAFTA in pivotal studies and an open-label extension study compared to propensity-score matched historical CFTR-modulator-untreated controls from the U.S. CFFPR (abstract WS22.04). Results show that TRIKAFTA demonstrated on average no decrease in ppFEV1 over a two-year period in this population, in contrast to declines seen in the matched controls. The analysis indicates that treatment with TRIKAFTA has a significant impact on the trajectory of CF lung disease.

Additionally, Vertex will present data from a long-term real-world study demonstrating that initiating KALYDECO (ivacaftor) early in life (ages 6-10 years) preserves lung function to a greater extent than if KALYDECO is initiated at an older age (abstract WS17.03). These results show the importance of early initiation of KALYDECO for eligible patients.

These long-term and real-world studies show the potentially transformative benefits of treatment with CFTR modulators and add to the substantial body of evidence supporting treatment as early in life as possible, said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. We continue to make rapid progress in developing medicines that treat the underlying cause of CF, and today, we are closer to our goal of developing highly effective therapies for all patients with CF than ever before.

Additional Presentations

In addition to the studies noted above, other Vertex presentations at the conference this year support the long-term and early use of CFTR modulators:

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes one from each parent to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing the CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.

About TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor) is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface by binding to different sites on the CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of elexacaftor, tezacaftor and ivacaftor help hydrate and clear mucus from the airways.

TRIKAFTA is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one copy of the F508del mutation, or another mutation responsive to TRIKAFTA, in the CFTR gene. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if TRIKAFTA is safe and effective in children under 6 years of age.

Please see Important Safety Information below and [click here] for full U.S. Prescribing Information.

About KALYDECO (ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein at the cell surface does not function properly. Known as a CFTR potentiator, ivacaftor is an oral medicine designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. KALYDECO (ivacaftor) was the first medicine to treat the underlying cause of cystic fibrosis (CF) in people with specific mutations in the CFTR gene.

KALYDECO is a prescription medicine used for the treatment of CF in patients aged 4 months and older who have at least one mutation in their CF gene that is responsive to KALYDECO. Patients should talk to their doctor to learn if they have an indicated CF gene mutation. It is not known if KALYDECO is safe and effective in children under 4 months of age.

Please see Important Safety Information below and [click here] for full U.S. Prescribing Information.

About ORKAMBI (lumacaftor/ivacaftor)

In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface.

ORKAMBI (lumacaftor/ivacaftor) is an oral medicine that is a combination of lumacaftor and ivacaftor. Lumacaftor is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del-CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of lumacaftor and ivacaftor help hydrate and clear mucus from the airways.

ORKAMBI is a prescription medicine used for the treatment of CF in patients age 2 years and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene. ORKAMBI should only be used in these patients. It is not known if ORKAMBI is safe and effective in patients under 2 years of age.

Please see Important Safety Information below and [click here] for full U.S. Prescribing Information.

IMPORTANT SAFETY INFORMATION for TRIKAFTA (elexacaftor/tezacaftor/ivacaftor and ivacaftor), KALYDECO (ivacaftor), and ORKAMBI (lumacaftor/ivacaftor)

Patients should not take KALYDECO or TRIKAFTA if they take certain medicines or herbal supplements, such as: the antibiotics rifampin or rifabutin; seizure medicines such as phenobarbital, carbamazepine, or phenytoin; or St. Johns wort.

Patients should not take ORKAMBI if they take certain medicines or herbal supplements, such as: the antibiotics rifampin or rifabutin; the seizure medicines phenobarbital, carbamazepine, or phenytoin; the sedatives and anti-anxiety medicines triazolam or midazolam; the immunosuppressant medicines cyclosporine, everolimus, sirolimus, or tacrolimus; or St. Johns wort.

Before taking KALYDECO, ORKAMBI, or TRIKAFTA patients should tell their doctor about all of their medical conditions, including if they: have or have had liver problems; have kidney problems; are pregnant or plan to become pregnant because it is not known if KALYDECO, ORKAMBI, or TRIKAFTA, will harm an unborn baby; or are breastfeeding or planning to breastfeed because it is not known if KALYDECO, ORKAMBI, or TRIKAFTA passes into breast milk. Before taking ORKAMBI, patients should tell their doctor if they have had an organ transplant, or if they are using a hormonal contraceptive including oral, injectable, transdermal, or implantable form as this should not be used as a method of birth control when taking ORKAMBI.

KALYDECO, ORKAMBI, or TRIKAFTA may affect the way other medicines work, and other medicines may affect how KALYDECO, ORKAMBI, or TRIKAFTA work. Therefore, the dose of KALYDECO, ORKAMBI, or TRIKAFTA may need to be adjusted when taken with certain medications. Patients should especially tell their doctor if they take antifungal medications such as ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole; or antibiotics such as telithromycin, clarithromycin, or erythromycin.

KALYDECO or TRIKAFTA can cause dizziness in some people who take it. Patients should not drive a car, use machinery, or do anything that needs them to be alert until they know how KALYDECO or TRIKAFTA affects them.

When taking ORKAMBI, patients should tell their doctor if they stop taking ORKAMBI for more than 1 week as their doctor may need to change the dose of ORKAMBI or other medicines the patient is taking.

Patients should avoid food or drink containing grapefruit while taking KALYDECO or TRIKAFTA.

KALYDECO, ORKAMBI, and TRIKAFTA can cause serious side effects, such as:

Liver damage and worsening of liver function in people taking TRIKAFTA with severe liver disease that can be serious and may require transplantation. Liver damage has also happened in people without liver disease.

High liver enzymes in the blood have been reported in patients receiving KALYDECO, ORKAMBI, or TRIKAFTA. The patient's doctor will do blood tests to check their liver before starting treatment with KALYDECO, ORKAMBI, or TRIKAFTA; every 3 months during the first year of treatment; and every year while on treatment. For patients who have had high liver enzymes in the past, the doctor may do blood tests to check the liver more often. Patients should call their doctor right away if they have any of the following symptoms of liver problems: pain or discomfort in the upper right stomach (abdominal) area; yellowing of their skin or the white part of their eyes; loss of appetite; nausea or vomiting; or dark, amber colored urine.

Worsening of liver function in people with severe liver disease taking ORKAMBI. The worsening of liver function can be serious or cause death. Talk to your doctor if you have been told you have liver disease as your doctor may need to adjust the dose of ORKAMBI.

Breathing problems such as shortness of breath or chest tightness in patients when starting ORKAMBI, especially in patients who have poor lung function. If a patient has poor lung function, their doctor may monitor them more closely when starting ORKAMBI.

An increase in blood pressure in some people receiving ORKAMBI. The patients doctor should monitor their blood pressure during treatment with ORKAMBI.

Abnormality of the eye lens (cataract) in some children and adolescents treated with KALYDECO, ORKAMBI, or TRIKAFTA. If the patient is a child or adolescent, their doctor should perform eye examinations before and during treatment with KALYDECO, ORKAMBI, or TRIKAFTA to look for cataracts.

The most common side effects of KALYDECO include headache; upper respiratory tract infection (common cold), which includes sore throat, nasal or sinus congestion, and runny nose; stomach (abdominal) pain; diarrhea; rash; nausea; and dizziness.

The most common side effects of ORKAMBI include breathing problems, such as shortness of breath and chest tightness; nausea; diarrhea; fatigue; increase in a certain blood enzyme called creatinine phosphokinase; rash; gas; common cold, including sore throat, stuffy or runny nose; flu or flu-like symptoms; and irregular, missed, or abnormal periods (menses) and increase in the amount of menstrual bleeding. Additional side effects seen in children include cough with sputum, stuffy nose, headache, stomach pain, and increase in sputum.

The most common side effects of TRIKAFTA include headache; diarrhea; upper respiratory tract infection (common cold), including stuffy and runny nose; stomach (abdominal) pain; inflamed sinuses; increase in liver enzymes; increase in a certain blood enzyme called creatine phosphokinase; rash; flu (influenza); and increase in blood bilirubin.

These are not all the possible side effects of KALYDECO, ORKAMBI, or TRIKAFTA. Please click product link to see the full U.S. Prescribing Information for KALYDECO, ORKAMBI, or TRIKAFTA.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes, alpha-1 antitrypsin deficiency and Duchenne muscular dystrophy.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 12 consecutive years on Science magazine's Top Employers list and one of the 2021 Seramount (formerly Working Mother Media) 100 Best Companies. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements made by Dr. Bozic in this press release, statements regarding the potential benefits, safety and efficacy of our products, and our plans to present data about our portfolio of CF products at the ECFS European Cystic Fibrosis Conference, including an analysis of data from the ongoing five-year post-authorization safety study for TRIKAFTA, data comparing the annual rate of lung function change in certain individuals with CF and our assessment of the impact of such data, data regarding the early initiation of KALYDECO and our assessment of the impact of such data, and additional scientific presentations regarding our marketed CF products, including expectations regarding the abstracts that will be made available at the ECFS European Cystic Fibrosis Conference. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration, approval or further development of its compounds due to safety, efficacy or other reasons, risks related to approval and commercialization of our medicines, and other risks listed under the heading Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission (SEC) and available through the company's website at http://www.vrtx.com and on the SECs website at http://www.sec.gov. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

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