On December 2, 2021 SQZ Biotechnologies Company (NYSE: SQZ), a cell therapy company developing novel treatments for multiple therapeutic areas, reported interim results from the highest-dose monotherapy cohort of its ongoing Phase 1/2 clinical trial of SQZ-PBMC-HPV, an investigational cell therapy being evaluated in certain patients with advanced or metastatic Human Papillomavirus positive (HPV16+) solid tumors (Press release, SQZ Biotech, DEC 2, 2021, View Source [SID1234596397]). In an abstract published today by the European Society for Medical Oncology Immuno-Oncology (ESMO-IO) Congress, taking place December 8-11, the company reported that a highly treatment experienced patient in the highest-dose cohort demonstrated a radiographic response in conjunction with substantial increases in CD8 T cell tumor infiltration and PD-L1 expression – both markers of tumor inflammation. The cell therapy was generally well tolerated and no dose limiting toxicities were observed in the final monotherapy stage of the trial.

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"We are excited to present detailed interim clinical findings from the highest dose monotherapy cohort of our ongoing SQZ-PBMC-HPV Phase 1/2 study at ESMO (Free ESMO Whitepaper)-IO," said Armon Sharei, Ph.D., Chief Executive Officer and Founder of SQZ Biotechnologies. "These data build upon the initial readout in lower dose cohorts presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual conference earlier this year. The latest clinical response data and biomarker findings further increase our enthusiasm for the SQZ APC program as we advance into the combination stage with checkpoint inhibitors."

Data on the highest dose cohort of SQZ-PBMC-HPV-101, including biomarker and tumor response findings, will be shared as an oral presentation at ESMO (Free ESMO Whitepaper)-IO on December 9. See presentation information below.

The combination stage of the trial is enrolling with checkpoint inhibitors targeting the PD-(L)1 and CTLA-4 pathways. Available clinical trial data and scientific literature suggest that SQZ APCs could work synergistically with checkpoint inhibitors due to their CD8 tumor infiltrating lymphocytes (TIL) driving mechanism.

Trial Highlights from ESMO (Free ESMO Whitepaper) IO Abstract 565

SQZ-PBMC-HPV-101 Phase 1/2 trial has four dose-escalating monotherapy cohorts ranging from 0.5 to 5.0 x10e6 cells per kg
A total of 18 patients were treated across four cohorts and patients had an average of 3.5 prior lines of systemic cancer therapy
Across all cohorts the investigational therapy was generally well-tolerated, and no dose-limiting toxicities were observed
No grade 2 or higher treatment-related severe adverse events, or grade 3 adverse events, were observed in the highest-dose cohort
In the highest-dose cohort with five patients evaluable, one patient who had been heavily treated with PD-1 inhibitors before entering the trial demonstrated radiographic response as well as substantial increases in CD8 T cell tumor infiltration and PD-L1 expression
The highest-dose monotherapy stage continues enrollment to further characterize the investigational therapy in single agent settings.

ESMO-IO Presentation Details

Oral Presentation: Thursday, December 9 at 12:10 pm CET
Presentation Number: 48MO
Abstract Title: SQZ-PBMC-HPV-101: Preliminary results of a first-in-human, dose-escalation study of a cell-based vaccine in HLA-A*02+ patients with recurrent, locally advanced, or metastatic HPV16+ solid tumors

Lead Author: Jong Chul Park, MD, Medical Oncologist and Investigator, Massachusetts General Hospital Cancer Center

The ESMO (Free ESMO Whitepaper)-IO presentation will be on the Events & Presentations section of the company’s website on December 9 at 12:10 pm CET.

Conference Call
The company will host a conference call and webcast at 8:00 a.m. ET on Thursday, December 9 to discuss the ESMO (Free ESMO Whitepaper)-IO presentation. Participants can join via webcast link or by dialing 1-877-805-7920 (domestic) or 1-629-228-0702 (international) five minutes prior to the start of the call. An archived webcast will be accessible for 90 days after the event.

SQZ-PBMC-HPV-101 Trial Design
SQZ-PBMC-HPV is being evaluated in a Phase 1/2 clinical trial for the treatment of HPV16+ advanced or metastatic solid tumors. Patients must be positive for the human leukocyte antigen serotype HLA-A*02. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immuno-oncology agents. The study’s primary outcome measures in the monotherapy and combination phases of the trial include safety and tolerability. Antitumor activity is a secondary outcome measure in both the monotherapy and combination stages of the trial, and manufacturing feasibility is a secondary outcome measure in the monotherapy phase of the trial. The monotherapy phase of the study includes escalating dose cohorts with a dose-limiting toxicity (DLT) window of 28 days and is designed to identify a recommended phase 2 dose. The planned combination phase of the study will include SQZ-PBMC-HPV and checkpoint inhibitors. DLT will be measured over 42 days.

About Human Papillomavirus Positive Cancers
Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer HPV+ tumors account for 4.5% of all cancers worldwide, resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

On December 2, 2021 Munich Reinsurance Company’s Canadian life branch (Munich Re) reported that partnership with the McGill University Health Centre (MUHC) Foundation to advance cutting-edge cardiovascular disease research (Press release, McGill University, DEC 2, 2021, View Source [SID1234596415]). As part of this partnership, Munch Re will help fund an innovative research project at the cutting-edge of science, MyHeart Counts Canada. In addition, Munich Re will collaborate with the project’s lead investigator, Abhinav Sharma MD, PhD., to incorporate an insurance cohort into the study to help fuel better outcomes for insured populations.

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MyHeart Counts is a revolutionary smartphone app created at Stanford University in the United States as part of a research study to understand better how to keep hearts healthy. It allows users to see how their physical activity and lifestyle affect their cardiovascular health by tracking their movement using their phone or wearable fitness tracker. The app then provides assessments that measure risk and teaches users how to improve their heart health.

Dr. Sharma, a cardiologist at the McGill University Health Centre (MUHC) in Montreal, was part of the Stanford team that created MyHeart Counts, and now he is bringing the app to Canadians. MyHeart Counts Canada will improve the heart health of Canadians from coast to coast while allowing Dr., Sharma and his team to gain a deeper understanding of the factors that lead to cardiovascular disease – one of the leading causes of death in Canada.

"Munich Re is proud to partner with the MUHC Foundation and support this innovative research project spearheaded by Dr. Sharma," said Bernard Naumann, President and CEO, Munich Re, Canada (Life). "The utilization of digital health technologies to improve cardiovascular health is an important area of interest for us. As one of the world’s leading life reinsurers, we constantly strive to improve our knowledge of cardiovascular disease in its myriad manifestations, and apply these advances in our risk assessment paradigm. We look forward to understanding how digital technologies will improve cardiovascular outcomes and ultimately both the quality of life and life expectancy"

Dr Sharma added, "I am grateful to Munich Re for supporting the development of MyHeart Counts Canada. Cardiovascular disease kills millions of people worldwide each year, and their generous support will help us better understand why heart disease develops and what we can do to prevent it."

"Munich Re’s investment in and support of MyHeart Counts Canada has the potential to change the lives of millions. While the app will benefit its users in the short term, the new insights into cardiovascular disease prevention will benefit everyone, now and in the future," commented Julie Quenneville, President, and CEO, McGill University Health Centre Foundation.

On December 2, 2021 Tune Therapeutics, a biotechnology company pioneering the creation of epi-therapeutic medicines, reported it launched with its powerful and precise genetic tuning platform, TEMPO (Press release, Tune Therapeutics, DEC 2, 2021, View Source [SID1234630692]). This cutting-edge technology dials gene expression up or down to desired levels – with the potential to reverse pathways of cancer, genetic disease, and aging by changing cell fate and function at will.

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"Genetic medicine is at a tipping point," said Matt Kane, CEO of Tune Therapeutics. "We now understand that the driving force of human health and disease is not our genes, but the epigenomic elements that shape and control them. Until now, scientists and bioengineers lacked the combined understanding, clinical expertise, and technology needed to make epigenomic therapies a practical reality. Now, we have all three."

TEMPO Platform

Tune’s proprietary TEMPO platform can rapidly target and adjust the epigenomic machinery of the cell, which shapes DNA and controls gene expression. By varying specific control modules in an iterative process, TEMPO can fine-tune expression toward healthy levels – even in diseases involving multiplex or polygenic interactions.

Unlike genome editing, the tuning process does not generate double- or single-strand breaks in DNA and makes no permanent changes to the DNA sequence. This de-risks the precise targeting of entire gene networks, allowing Tune to simultaneously turn silenced genes on and dial over-expressed genes down, in a practical, therapeutic context.

Tune has already shown that TEMPO can locate epigenomic elements involved in several intractable genetic conditions – revealing targets and networks that would be invisible or inaccessible to gene editing approaches. Moreover, Tune can optimize TEMPO to command expression of individual genes or networks with remarkable specificity and precision. This opens the door to an entirely new class of epi-therapeutics.

"The exciting challenge in front of us is taking these transformative advances in technology and extending their potential for our greater society," said Charlie Gersbach, PhD, Acting Chief Scientific Officer, Tune Therapeutics. "From proof of concept in rare, single-gene disorders to common conditions that aren’t linked to a single gene mutation – but are treatable through epigenomic control and constitute the vast majority of human diseases."

Veteran Genomic Medicine Leadership Team

Tune is launching with a veteran leadership team, endowed with deep expertise in gene and cell therapy, genome editing, and epigenetics.

Matt Kane, Chief Executive Officer
Akira Matsuno, Co-Founder, President and Chief Financial Officer
Charlie Gersbach, Ph.D., Co-Founder, Acting Chief Scientific Officer
Fyodor Urnov, Ph.D., Co-Founder, Scientific Advisory Board
Heidi Zhang, Ph.D., Executive Vice President, Head of Technical Operations
Blythe Sather, Ph.D., Vice President, Head of Research
In addition, Tune’s Board of Directors includes Mr. Kane, Dr. Gersbach, Ali Behbahani, M.D., (New Enterprise Associates), and co-founder Dan McHugh (Emerson Collective).

Drawing upon deep, local talent pools in Durham and Seattle, Tune has assembled two highly seasoned discovery and development teams, secured foundational intellectual property from Duke University, and raised $40 million from top-tier investors – including co-leads New Enterprise Associates and Emerson Collective, with Hatteras Venture Partners, Mission BioCapital, and others joining the round. This financing will enable Tune to rapidly advance its preclinical research, attract top-tier talent, and further develop its therapeutic platform.

"Tune is effectively pioneering a brand-new therapeutic modality," said Dr. Behbahani. "With the unbound potential of this approach, and their collective successes in the field, Tune is primed to become a transformative presence in modern biomedicine."

On December 2nd, 2021 BioRay Pharmaceutical Co., Ltd. (hereinafter referred to as "BioRay") reported that the first patient with Primary immunologic thrombocytopenic purpura (ITP) had been dosed in the Phase II Clinical trial of self-developed Zuberitamab (development code: HS006) (Press release, Zhejiang Hisun Pharmaceutical, DEC 2, 2021, View Source;a=index&classid=43&id=3 [SID1234634620]). The study aims to evaluate the safety and efficacy of Zuberitamab (HS006) in subjects with primary persistent or chronic ITP who failed from prior therapy(ies). The leading entity of the clinical trial is Tongji Medical College, Union Hospital, Huazhong University of Science and Technology and the principal investigator is Prof.Yu Hu.

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Zuberitamab (HS006) is a human-mouse chimeric monoclonal antibody that specifically binds to B-lymphocyte antigen CD20 and can kill B cells via ADCC and CDC action. Zuberitamab (HS006) has demonstrated a favorable safety and efficacy profile in B-cell lymphoma in clinical trials. As B cells play an important role in the pathogenesis of autoimmune diseases such as primary immunologic thrombocytopenic purpura (ITP), rheumatoid arthritis (RA), and multiple sclerosis (MS), Zuberitamab (HS006) has the potential to be used in the treatment of autoimmune diseases.

Primary immunologic thrombocytopenic purpura (ITP) is an acquired autoimmune disease characterized by thrombocytopenia. The pathogenesis of ITP is mainly due to the loss of immune tolerance to the patient’s platelet membrane antigens. The patient’s B cells produce antibodies against different platelet antigens, leading to the formation of antigen-antibody complexes, and resulting in excessive destruction of platelets in the spleen or liver. Meanwhile, thrombopoiesis is impaired. Zuberitamab (HS006) specifically clears B-lymphocytes, thereby reducing autoantibody production and platelet destruction. Zuberitamab (HS006) is expected to bring an alternative treatment optionfor ITP patients and improve their quality of life.

"Zuberitamab (HS006) is a self-developed monoclonal antibody that targets the CD20 protein on the surface of B cells. It can rapidly, thoroughly and durably remove CD20+ B cells, and this effect is reversible after drug withdrawal, " said by Dr. Haibin Wang, the Chief Medical Officer (CEO) of BioRay, "The Phase III Clinical trial of Zuberitamab (HS006) for primary treatment of diffuse large B-cell lymphoma has completed the observation of the primary endpoint, and the study results confirmed its good safety, tolerability and efficacy, which provides strong support for the subsequent clinical development of ITP. Based on the existing achievements, BioRay will make every effort to promote its clinical research in ITP and other diseases and promote the early launch of this product in China to benefit more patients."

On December 2, 2021 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported the completion of patient recruitment in the Phase 3 SIENDO study evaluating the efficacy and safety for front-line maintenance therapy with selinexor in patients with advanced or recurrent endometrial cancer (Press release, Karyopharm, DEC 2, 2021, View Source [SID1234596398]).

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Endometrial cancer is the most common cancer of the female reproductive organs, with more than 66,000 new cases in the US in 2021.1 Unfortunately, prognosis is poor with an estimated 14,000 women progressing to advanced disease.2 There are currently no approved therapies in the maintenance setting for patients with advanced or recurrent endometrial cancer.

"There is a clear and significant need for treatments that help extend remission or delay disease progression following front-line chemotherapy treatment in patients with endometrial cancer," said Sharon Shacham, PhD, Chief Scientific Officer of Karyopharm. "Completing enrollment in the Phase 3 SIENDO study is an important step toward our goal of delivering a novel, front-line maintenance therapy for patients and positive data from this study will further reinforce our views on the therapeutic potential of selinexor in solid tumor indications. We anticipate reporting top-line data from this event-driven study by the end of this year or early next year."

The SIENDO study has exceeded its enrollment goal, with over 250 patients currently enrolled or in screening. The SIENDO study is a multicenter, blinded, placebo-controlled, randomized Phase 3 study evaluating the efficacy and safety for maintenance therapy with selinexor in patients with advanced or recurrent endometrial cancer. Participants with primary stage IV or recurrent disease who had a partial or complete response after a single line of at least 12 weeks of standard taxane-platinum combination chemotherapy are randomized in a 2:1 manner to receive either maintenance therapy of 80mg of selinexor taken once per week or placebo, until disease progression. The primary endpoint in the study is progression free survival with the goal of the study demonstrating a hazard ratio of 0.6.

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein exportin 1 (XPO1, also called CRM1). XPOVIO blocks the nuclear export of tumor suppressor, growth regulatory and anti-inflammatory proteins, leading to accumulation of these proteins in the nucleus and enhancing their anti-cancer activity in the cell. The forced nuclear retention of these proteins can counteract a multitude of the oncogenic pathways that, unchecked, allow cancer cells with severe DNA damage to continue to grow and divide in an unrestrained fashion. Karyopharm received accelerated U.S. Food and Drug Administration (FDA) approval of XPOVIO in July 2019 in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. NEXPOVIO (selinexor) has also been granted conditional marketing authorization for adult patients with heavily pretreated multiple myeloma by the European Commission. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA on December 18, 2020. In June 2020, Karyopharm received accelerated FDA approval of XPOVIO for its second indication in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple cancer indications, including as a potential backbone therapy in combination with approved myeloma therapies (STOMP) and in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

For more information about Karyopharm’s products or clinical trials, please contact the Medical Information department at:

Tel: +1 (888) 209-9326
Email: [email protected]

XPOVIO (selinexor) is a prescription medicine approved:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy (XVd).
In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti–CD38 monoclonal antibody (Xd).
For the treatment of adult patients with relapsed or refractory diffuse large B–cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
SELECT IMPORTANT SAFETY INFORMATION

Warnings and Precautions

Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care.
Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony–stimulating factors.
Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care.
Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care.
Serious Infection: Monitor for infection and treat promptly.
Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes.
Embryo–Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception.
Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract.
Adverse Reactions

The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3–4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%.
The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%.
The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3–4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients.
Use In Specific Populations
Lactation: Advise not to breastfeed.

For additional product information, including full prescribing information, please visit www.XPOVIO.com.