On May 19, 2021 Jasper Therapeutics, Inc., a biotechnology company focused on hematopoietic cell transplant therapies, reported updated 90-day efficacy, safety and pharmacokinetic data from its ongoing multicenter Phase 1 clinical trial of JSP191, the company’s first-in-class anti-CD117 monoclonal antibody, as a targeted, non-toxic conditioning regimen in older patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) undergoing allogeneic hematopoietic (blood) cell transplantation (Press release, Jasper Therapeutics, MAY 19, 2021, View Source [SID1234580304]). Data from the dose-finding part of the study showed that conditioning with a single dose of JSP191 0.6 mg/kg prior to low dose radiation and fludarabine in preparation for transplantation was well tolerated in all six patients and led to successful transplant as evidenced by full chimerism and elimination of measurable residual disease (MRD) in five of six patients. The findings will be presented by lead investigator Lori Muffly, M.D., M.S., Assistant Professor of Medicine (Blood and Bone Marrow Transplantation) at Stanford Medicine, in a poster session at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held online from June 4-8. The abstract is available now on the ASCO (Free ASCO Whitepaper) Annual Meeting website.

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"We are very encouraged by the updated efficacy and safety results from this Phase 1 clinical study, which is the first to evaluate JSP191 in combination with non-myeloablative conditioning for older patients with MDS or AML. These data are consistent with pre-clinical work that demonstrated the capacity of JSP191 to target myelodysplastic cells and synergize with low doses of radiation. While hematopoietic cell transplantation is curative in these patients, its use is limited in older and frail patients because of the toxicity associated with standard-of-care myeloablative conditioning agents," said Kevin N. Heller, M.D., Executive Vice President, Research and Development, of Jasper Therapeutics. "Based on this data and feedback from the FDA, we have now opened the dose-expansion phase of the study at the recommended Phase 2 dose. We anticipate announcing topline data in the first half of next year. We continue to evaluate JSP191 as a conditioning agent in multiple additional diseases, including our ongoing clinical trial in severe combined immunodeficiency (SCID), our upcoming study in refractory autoimmune disease and with our partnerships with the NIH and Stanford in sickle cell disease and Fanconi anemia. We believe that JSP191 addresses key limitations of current conditioning regimens and potentially may expand the number of patients with devastating diseases who could be cured with hematopoietic stem cell therapy."

At 90 days after transplant, MRD as measured by cytogenetics, karyotype and next-generation sequencing was negative (undetected) in five patients and reduced in one patient, and full chimerism (greater than 95%) was observed in five of the six patients. One patient had secondary graft failure with no evidence of relapse at 90 days. JSP191, when added to low-dose radiation and fludarabine, was well tolerated in all six patients; the protocol allows for subjects to receive the conditioning regimen in an outpatient setting. No infusion reactions, treatment-related toxicities such as oral mucositis or evidence of acute graft versus host disease were reported. Pharmacokinetic data showed that serum levels of the JSP191 0.6 mg/kg dose were consistent among study participants as evaluated up to 14 days post-infusion.

Phase 1 Study Design

The open-label, multicenter Phase 1 study (JSP-CP-003) is evaluating the safety, tolerability and efficacy of adding JSP191 to the standard conditioning regimen of low-dose radiation and fludarabine among patients age 65 to 74 years with MDS or AML undergoing hematopoietic cell transplantation. Patients were ineligible for full myeloablative conditioning. The primary outcome measure of the study is the safety and tolerability of JSP191 as a conditioning regimen up to one year following a donor cell transplant. Secondary endpoints include engraftment and donor chimerism, MRD clearance, non-relapse mortality, event-free survival and overall survival.

About MDS and AML

Myelodysplastic syndromes (MDS) are a group of disorders in which immature blood-forming cells in the bone marrow become abnormal and do not make new blood cells or make defective blood cells, leading to low numbers of normal blood cells, especially red blood cells.i In about one in three patients, MDS can progress to acute myeloid leukemia (AML), a rapidly progressing cancer of the bone marrow cells.i Both are diseases of the elderly with high mortality. Each year, about 29,000 patients are diagnosed with MDS and approximately 42,000 patients are diagnosed with AML in the G7 countries for which approximately 2,500 patients with MDS and approximately 8,000 people with AML receive hematopoietic stem cell transplants. These transplants are curative but are underused due to the toxicity of the current high-intensity conditioning regimen, which includes the chemotherapy agents busulfan and fludarabine.

About JSP191

JSP191 is a first-in-class humanized monoclonal antibody in clinical development as a conditioning agent that blocks stem cell factor receptor signaling leading to clearance of hematopoietic stem cells from bone marrow, creating an empty space for donor or gene-corrected transplanted stem cells to engraft. To date, JSP191 has been evaluated in more than 90 healthy volunteers and patients. Jasper is currently enrolling in two clinical trials for acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS) and severe combined immunodeficiency (SCID) and expects to begin enrollment in three additional studies in 2021 for severe autoimmune disease, sickle cell disease and Fanconi anemia patients undergoing hematopoietic cell transplantation.

On May 19, 2021 ADC Therapeutics SA (NYSE:ADCT), a commercial-stage biotechnology company leading the development of novel antibody drug conjugates (ADCs) to treat hematological malignancies and solid tumors, announced today three abstracts have been selected for poster presentations at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is being held virtually June 4-8, 2021 (Press release, ADC Therapeutics, MAY 19, 2021, View Source [SID1234580320]).

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"We are pleased that research from our lead programs will be shared with the oncology community at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting," said Jay Feingold, MD, PhD, Senior Vice President and Chief Medical Officer of ADC Therapeutics. "On the heels of the accelerated FDA approval of ZYNLONTA (loncastuximab tesirine-lpyl), we continue to advance our deep pipeline to deliver next-generation ADC therapies to patients with hematologic and solid tumor cancers."

Poster Presentation Details

Title: Duration of response to loncastuximab tesirine in relapsed/refractory diffuse large B-cell lymphoma by demographic and clinical characteristics: Subgroup analyses from LOTIS 2
Track: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Date/Time: On demand beginning June 4 at 9 a.m. EDT
Presenter: Paolo F. Caimi, MD, University Hospitals Cleveland Medical Center and Case Comprehensive Cancer Center, Case Western Reserve University
Abstract Number: 7546

Title: Phase 3 randomized study of loncastuximab tesirine plus rituximab versus immunochemotherapy in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): LOTIS-5
Track: Hematologic Malignancies – Lymphoma and Chronic Lymphocytic Leukemia
Date/Time: On demand beginning June 4 at 9 a.m. EDT
Presenter: Mehdi Hamadani, MD, Professor of Internal Medicine at the Medical College of Wisconsin, Division of Hematology & Oncology
Abstract Number: TPS7574

Title: A Phase 1b, open-label, dose-escalation study to evaluate camidanlumab tesirine (Cami) as monotherapy in patients (pts) with advanced solid tumors
Track: Developmental Therapeutics—Immunotherapy
Date/Time: On demand beginning June 4 at 9 a.m. EDT
Presenter: Igor Puzanov, MD, Clinical Professor of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo
Abstract Number: 2556

About ZYNLONTA (loncastuximab tesirine-lpyl)

ZYNLONTA is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) has approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. This indication is approved by the FDA under accelerated approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The FDA approval was based on data from LOTIS-2, a large (n=145) Phase 2 multinational, single-arm clinical trial of ZYNLONTA for the treatment of adult patients with r/r DLBCL following two or more prior lines of systemic therapy. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with very difficult to treat disease, including patients with high-grade B-cell lymphoma. The trial also enrolled patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, and patients who had stem cell transplants and CAR-T therapy prior to their treatment with ZYNLONTA. Results from the trial demonstrated an overall response rate (ORR) of 48.3% (70/145 patients), which included a complete response (CR) rate of 24.1% (35/145 patients) and a partial response (PR) rate of 24.1% (35/145 patients). Patients had a median time to response of 1.3 months. At the most recent data cut-off for patients enrolled in the trial, the median duration of response (mDoR) was 12.58 months. In a pooled safety population the most common adverse reactions (≥20%) were thrombocytopenia, gamma-glutamyltransferase increased, neutropenia, anemia, hyperglycemia, transaminase elevation, fatigue, hypoalbuminemia, rash, edema, nausea and musculoskeletal pain. In LOTIS-2, the most common (≥10%) grade ≥3 treatment-emergent adverse events were neutropenia (26.2%), thrombocytopenia (17.9%), gamma-glutamyltransferase increased (17.2%) and anemia (10.3%).

ZYNLONTA is being evaluated in combination for earlier lines of therapy and as a monotherapy in other B-cell malignancies.

About Camidanlumab Tesirine (Cami)

Camidanlumab tesirine (Cami, formerly ADCT-301) is an antibody drug conjugate (ADC) comprised of a monoclonal antibody that binds to CD25 (HuMax-TAC, licensed from Genmab A/S), conjugated to the pyrrolobenzodiazepine (PBD) dimer payload, tesirine. Once bound to a CD25-expressing cell, Cami is internalized into the cell where enzymes release the PBD-based payload killing the cell. This applies to CD25-expressing tumor cells, and also to CD25-expressing Tregs. The intra-tumoral release of its PBD payload may also cause bystander killing of neighboring tumor cells and PBDs have also been shown to induce immunogenic cell death. All of these properties of Cami may enhance immune-mediated anti-tumor activity.

Cami is being evaluated in a pivotal Phase 2 clinical trial in patients with relapsed or refractory Hodgkin lymphoma (HL), as well as in a Phase 1a/1b clinical trial in patients with relapsed or refractory HL and non-Hodgkin lymphoma and a Phase 1b clinical trial as monotherapy and in combination with pembrolizumab in solid tumors.

On May 19, 2021 PTC Therapeutics, Inc. (NASDAQ: PTCT) reported that management will present a company overview at the following conference (Press release, PTC Therapeutics, MAY 19, 2021, View Source [SID1234580419]):

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William Blair 41st Annual Growth Stock Conference
Wednesday, June 2nd at 3:40 p.m. ET

The presentation will be webcast live on the Events and Presentations page under the investor relations section of PTC Therapeutics’ website at View Source and will be archived for 30 days following the presentation. It is recommended that users connect to PTC’s website several minutes prior to the start of the webcast to ensure a timely connection.

On May 19, 2021 NuCana plc (NASDAQ: NCNA) reported that financial results for the first quarter ended March 31, 2021 and provided an update on its broad clinical program with its transformative ProTide therapeutics (Press release, Nucana BioPharmaceuticals, MAY 19, 2021, View Source [SID1234584207]).

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As of March 31, 2021, NuCana had cash and cash equivalents of £78.6 million compared to £87.4 million as of December 31, 2020. NuCana continues to advance its various clinical programs and reported a net loss of £9.8 million for the quarter ended March 31, 2021, as compared to a loss of £4.0 million for the quarter ended March 31, 2020. Basic and diluted loss per share was £0.19 for the quarter ended March 31, 2021, as compared to £0.12 per share for quarter ended March 31, 2020.

"We are very pleased with our momentum in 2021," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "In January, we presented data at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (ASCO-GI) from the NuTide:302 study demonstrating NUC-3373’s encouraging efficacy signals and favorable safety profile in patients with advanced colorectal cancer. Among the efficacy-evaluable population, a disease control rate of 62% was achieved. In addition, NUC-3373 was well tolerated with no hand-foot syndrome or neutropenia as well as lower rates of diarrhea, mucositis and stomatitis as compared to historical data for 5-FU and capecitabine in the frontline treatment of patients with colorectal cancer."

Mr. Griffith continued: "In April, we were excited to present five posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. NUC-3373 maintained the encouraging 62% disease control rate in the efficacy-evaluable population in the NuTide:302 study. The poster also detailed three patients who experienced reductions in their target lesions of 40%, 28% and 15% and several patients who achieved a longer progression-free survival on NUC-3373 than they had on their prior therapy. We also presented additional clinical data from the ongoing Phase I study of NUC-7738. These data demonstrated NUC-7738’s encouraging anti-cancer activity and favorable tolerability profile. Three case studies described patients who achieved tumor volume reductions and prolonged stable disease on NUC-7738. Other AACR (Free AACR Whitepaper) posters showed NUC-3373-treated colon cancer cells are able to activate a natural killer cell response and described how NUC-7738 was designed to overcome the key cancer resistance mechanisms which have prevented the clinical development of its parent nucleoside analog, 3’-deoxyadenosine. Overall, these presentations highlighted the potential of our ProTides to significantly improve the treatment outcomes for patients with cancer."

Mr. Griffith concluded: "We are excited with the progress we have made so far in 2021. We remain focused on continuing to drive recruitment across all of our ongoing studies, including our Phase III study of Acelarin plus cisplatin in patients with biliary tract cancer as well as initiating new studies, including our second Phase III study evaluating NUC-3373 in combination with other agents for patients with colorectal cancer. We look forward to providing additional updates as we go through 2021."

Anticipated 2021 Milestones

Acelarin is a ProTide transformation of gemcitabine. In 2021, NuCana expects to:
Complete recruitment sufficient to enable the first interim analysis in 2022 of the Phase III study of Acelarin combined with cisplatin as a first-line treatment for patients with advanced biliary tract cancer.

NUC-3373 is a ProTide transformation of the active anti-cancer metabolite of 5-FU. In 2021, NuCana expects to:
Report data from the Phase Ib study (NuTide:302) of NUC-3373 in combination with other agents with which 5-FU is typically combined, such as leucovorin, oxaliplatin and irinotecan in patients with advanced colorectal cancer;
Initiate and report data from a Phase Ib expansion / Phase II study of NUC-3373 in combination with other agents for patients with colorectal cancer;
Initiate a Phase III study of NUC-3373 in combination with other agents for patients with colorectal cancer; and
Report data from the Phase I study (NuTide:301) of NUC-3373 in patients with advanced solid tumors.

NUC-7738 is a ProTide transformation of a novel nucleoside analog, 3’-deoxyadenosine. In 2021, NuCana expects to:
Report data from the Phase I study (NuTide:701) of NUC-7738 in patients with advanced solid tumors; and
Initiate a Phase II study of NUC-7738 in patients with solid tumors.

On May 19, 2021 Silence Therapeutics plc, AIM:SLN and Nasdaq: SLN ("Silence" or "the Company"), a leader in the discovery, development and delivery of novel short interfering ribonucleic acid (siRNA) therapeutics for the treatment of diseases with significant unmet medical need, reported positive topline data from the GEMINI phase 1 study of its wholly owned product candidate, SLN124, in healthy volunteers (Press release, Silence Therapeutics, MAY 19, 2021, View Source [SID1234580240]). SLN124, an siRNA which targets TMPRSS6, is in development for the treatment of iron-loading anemia conditions, thalassemia and myelodysplastic syndrome (MDS).

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The GEMINI phase 1, randomized, double-blind, placebo-controlled, single-ascending dose study evaluated the safety and tolerability of SLN124 (1.0, 3.0 and 4.5 mg/kg doses) in 24 healthy volunteers (18 active and 6 placebo). Pharmacokinetic parameters and pharmacodynamic biomarkers of iron metabolism were also measured to assess reduction in iron.

Initial data from the study showed all doses of SLN124 were generally well-tolerated with no serious or severe treatment emergent adverse events (TEAEs) or TEAEs leading to withdrawal. TEAEs did not appear to be dose dependent and the majority were mild, including transient injection site reactions which resolved without intervention.

Notably, up to an approximate four-fold increase in average hepcidin and 50% reduction in plasma iron levels were also observed after a single dose of SLN124. Effects on hepcidin and iron appear to be dose dependent and were still observed at the end of the 8-week study at all dose levels, indicating a sustained and long duration of action.

These clinical data support preclinical findings which demonstrated SLN124 effectively improved red blood cell production and reduced anemia by increasing levels of hepcidin – a key natural regulator of iron balance and distribution in the body. The Company expects to measure red blood cell production and effects on anemia in the ongoing GEMINI II phase 1 study of SLN124 in people with thalassemia and MDS, who unlike healthy volunteers have significantly elevated iron levels.

Mark Rothera, President and CEO of Silence Therapeutics, said: "These data represent the first clinical data from our mRNAi GOLD platform and underscore the promising potential for our technology to deliver precision medicines. We look forward to further data in patients anticipated from both of our wholly owned clinical programs later this year – the GEMINI II study of SLN124 for iron-loading anemia conditions and the APOLLO study of SLN360 for cardiovascular disease due to high lipoprotein(a)."

Giles Campion, M.D., EVP, Chief Medical Officer and Head of Research & Development of Silence Therapeutics, said: "Today’s results confirm the strong preclinical profile of SLN124 in humans – we observed excellent safety, robust gene knockdown expressed by up to an approximate four-fold increase in average hepcidin along with a 50% reduction in serum iron levels and a durable effect which lasted throughout the study. We are encouraged by these data in healthy volunteers and the opportunity for SLN124 to potentially address iron-loading anemia conditions such as thalassemia and MDS."

John Porter, M.D., Professor and Consultant Haematologist, Red Cell Disorders Unit, University College London and University of College London Hospitals, commented: "Despite advances in our understanding of thalassemia and MDS, there are no existing treatments that specifically target the underlying mechanisms of these conditions as a way to improve the degree of anemia. There is a major unmet need for a therapy that can provide safe and continuous control of iron balance and distribution as a way to improve the efficiency of red cell production. I’m encouraged by data from the SLN124 study in healthy volunteers and look forward to further clinical testing."

Silence expects to present full data from the GEMINI phase 1 study of SLN124 in healthy volunteers at an appropriate scientific meeting later this year. In addition, the Company plans to report data from the single-ascending dose portion of the ongoing GEMINI II phase 1 study of SLN124 in people with thalassemia and MDS in the second half of this year. SLN124 has Orphan Drug Designation for both conditions and rare pediatric disease designation for beta thalassemia.

About Thalassemia and Myelodysplastic Syndrome (MDS)
Thalassemia and MDS are both rare diseases that prevent a person from producing enough healthy red blood cells. Low levels of healthy red blood cells, known as anemia, result in less oxygen being delivered to different parts of the body. This can cause symptoms such as excessive tiredness and weakness. It can also lead to other serious health problems, such as heart disease. People living with thalassemia or MDS can also store too much iron in their bodies, leading to a phenomenon called ‘iron overload’, which damages organs such as the heart and liver.

Both conditions are typically treated with regular blood transfusions, which add to the problem of iron overload. Iron chelation therapy removes excess iron from the body using special medicines. While it helps reduce the amount of iron in the blood for people with thalassemia or MDS, it does not treat the underlying cause of the condition or stop it from progressing. There is, therefore, a need for therapies that directly address the biological drivers of disease.

About SLN124
SLN124 is a gene ‘silencing’ therapy – one that is designed to temporarily block a specific gene’s message that would otherwise trigger an unwanted effect. In this case, SLN124 aims to temporarily ‘silence’ TMPRSS6, a gene that prevents the liver from producing a particular hormone that controls iron levels in the body – hepcidin. As hepcidin increases, it is hoped that iron levels in the blood will decrease, which could in turn allow more healthy red blood cells to be produced, thereby improving anemia. In preclinical studies, SLN124 has shown positive effects on improving levels of red blood cells and reducing harmful iron levels.

SLN124 is now being studied in the GEMINI clinical trial program. GEMINI II is a phase 1 study to investigate the effects of SLN124 in people with thalassemia or myelodysplastic syndrome (MDS), whose bodies produce fewer healthy red blood cells than normal and who can store too much iron in their bodies. For more information on the GEMINI II study, please click here.