Shattuck Labs to Present at TIGIT Therapies Digital Summit 2021

On December 2, 2021 Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease with three ongoing Phase 1 clinical trials, reported its presentation at the TIGIT Therapies Digital Summit 2021 being held virtually December 7 – 9, 2021 (Press release, Shattuck Labs, DEC 2, 2021, View Source [SID1234596402]).

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Presentation Details
Presentation Title: LIGHTing the Way for TIGIT Blockade in CPI Refractory Tumors
Presenter: Taylor Schreiber, M.D., Ph.D., Shattuck’s Chief Executive Officer
Date: December 9, 2021
Time: 9:30 a.m. EST
Location: View Source

The presentation will be available for download on the Events & Presentations section of the company’s website and also will be available to registered participants of the TIGIT Therapies Digital Summit 2021.

Veru Reports Record Fiscal 2021 Full-Year Financial Results

On December 2, 2021 Veru Inc. (NASDAQ: VERU), an oncology biopharmaceutical company with a focus on developing novel medicines for the management of breast and prostate cancer, reported that fiscal 2021 full-year net revenues increased 44% to $61 million and gross profit increased 56% to $48 million, achieving new historical highs (Press release, Veru, DEC 2, 2021, View Source [SID1234596401]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Fourth-Quarter Financial Highlights: Fiscal 2021 vs Fiscal 2020

Net revenues increased 33% to $15.6 million from $11.7 million
FC2 prescription net revenues climbed 55% to $13.6 million from $8.7 million
Gross profit rose 29% to $12.3 million from $9.6 million
Gross margin was 79% of net revenues compared with 81% of net revenues
Operating loss was $1.9 million versus $11.3 million. Operating loss in the fiscal 2020 period included a $14.1 million non-cash impairment charge.
Net loss was $4.3 million, or $0.05 per share, compared with $11.8 million, which included a non-cash impairment charge of $14.1 million related to intangible assets or $0.17 per share.
Full-Year Financial Highlights: Fiscal 2021 vs Fiscal 2020

Net revenues increased 44% to $61.3 million from $42.6 million, a record high when compared to any prior fiscal year
FC2 prescription net revenues climbed 71% to $46.5 million from $27.1 million
Gross profit rose 56% to $47.9 million from $30.8 million
Gross margin increased to 78% of net revenues from 72% of net revenues
Operating income was $13.0 million, which included an $18.4 million gain on the December 2020 sale of the PREBOOST business, compared with operating loss of $14.7 million, which included the $14.1 million non-cash impairment charge.
Net income, which included the gain on the sale of the PREBOOST business, was $7.4 million and diluted EPS was $0.09 compared with net loss of $19.0 million and diluted loss per share of $0.28, which included the non-cash impairment charge.
Balance Sheet Information

Cash and cash equivalents were $122.4 million as of September 30, 2021 versus $13.6 million as of September 30, 2020
Net accounts receivable were $8.8 million as of September 30, 2021 versus $5.2 million as of September 30, 2020
"Once again we’ve reported new historical highs for full fiscal year net revenues and gross profit based on the robust growth of our US FC2 prescription business," said Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer of Veru Inc. "On a sobering note, US and global COVID-19 hospitalizations and deaths are on the rise again. The identification of the omicron variant and the possibility that the current vaccines and antibody drugs may not be as effective against this variant means that drugs to treat severe COVID-19 are desperately needed. The mechanism of drug action of sabizabulin is that it disrupts microtubule intracellular transport of the coronavirus, a process that will still be required by new variants or strains of COVID-19, including omicron, to cause infection. While there have been recent developments evaluating molnupiravir and PAXLOVID (PF-07321332; ritonavir) for the treatment of unhospitalized patients with mild to moderate COVID-19 at a relatively lower risk of dying, sabizabulin is being developed for hospitalized patients with a high risk of death. In our positive Phase 2 clinical study in hospitalized COVID-19 patients at risk for acute respiratory distress syndrome, sabizabulin treatment resulted in an 82% relative reduction in death compared to placebo. If our Phase 2 clinical results are replicated to any significant degree in our global Phase 3 clinical study, we believe sabizabulin would fill a significant current unmet medical need for hospitalized patients. In our global Phase 3 clinical study of sabizabulin we are enrolling 300 hospitalized patients with moderate to severe COVID-19 who are at high risk for Acute Respiratory Distress Syndrome. We expect to have clinical results in the first half of calendar 2022.

"These strong financial results have also enabled us to continue to advance our deep late clinical stage drug pipeline portfolio. We are heavily committed to developing our drug candidate assets in breast and prostate cancer. In our breast cancer program, we are addressing 3rd line treatment of ER+ metastatic breast cancer through two separate studies with patient populations depending on the AR expression in the breast cancer tissue. Targeting patients whose AR expression in breast cancer is ≥ 40% AR, we are enrolling the Phase 3 ARTEST clinical study to evaluate enobosarm monotherapy. Targeting patients whose AR breast cancer expression is <40%, we plan to conduct a Phase 2b clinical study of sabizabulin monotherapy. We are also moving enobosarm earlier in the treatment sequence to the 2nd line treatment of AR+ER+ metastatic breast cancer by targeting patients with AR breast cancer expression ≥ 40% in the Phase 3 ENABLAR-2 study. The Phase 3 ENABLAR-2 study will evaluate the efficacy and safety of enobosarm and CDK 4/6 inhibitor combination. Finally, for AR+ metastatic triple negative breast cancer, we plan to conduct a single arm Phase 2 clinical study evaluating the combination of enobosarm and sabizabulin treatment in patients who have progressed after receiving at least 2 systemic chemotherapies. Because of the importance of determining the patient’s AR status and based on the recommendation of FDA, we will develop a companion diagnostic AR test. We are pleased to be partnering with Roche/Ventana Diagnostics, a global oncology diagnostics company, who will develop and, if approved, commercialize a companion diagnostic AR test.

"In our prostate cancer program, we are enrolling our Phase 3 VERACITY clinical study of sabizabulin for metastatic castration and androgen receptor targeting agent resistant prostate cancer, but prior to IV chemotherapy. We are also enrolling our Phase 2 dose-finding clinical study of VERU-100, a novel long-acting GnRH antagonist 3-month depot injection formulation for androgen deprivation therapy for hormone sensitive advanced prostate cancer. Once completed, we will start the Phase 3 registration study.

"Finally, our Sexual Health division, led by robust FC2 sales, and if approved this month, the addition of ENTADFI sales expected in the first half of calendar year 2022, we will continue to have substantial resources to invest in our premium oncology drug pipeline line which is dedicated to addressing significant unmet medical needs for two of the most prevalent cancers, prostate and breast cancer. I am pleased and excited with Veru’s transformation into a premium oncology biopharmaceutical company seeking large market opportunities. The Company remains duty-bound during this persistent global pandemic to pursue this COVID-19 indication even though it is not the primary focus of the Company."

Pharmaceutical Pipeline Highlights:

Breast Cancer Program

Enobosarm, a Novel Oral Selective Androgen Receptor Targeted Agonist, for the 3rd Line Treatment of Androgen Receptor Positive (AR+), Estrogen Receptor Positive (ER+) and Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Metastatic Breast Cancer with AR ≥ 40% – Phase 3 ARTEST Clinical Study- Enrolling.

Enobosarm is the first new class of targeted endocrine therapy in advanced breast cancer in decades. Enobosarm is an oral, new chemical entity, selective androgen receptor agonist that targets the androgen receptor, a tumor suppressor, in AR+ER+HER2- metastatic breast cancer without the unwanted masculinizing side effects. Enobosarm has extensive nonclinical and clinical experience having been evaluated in 25 separate clinical studies in over 2,000 patients including three Phase 2 clinical studies in advanced breast cancer involving more than 250 patients. In the two Phase 2 clinical studies conducted in women with AR+ER+HER2- metastatic breast cancer, enobosarm demonstrated significant antitumor efficacy in heavily pretreated cohorts that failed estrogen receptor targeting agents, chemotherapy, and/or CDK 4/6 inhibitors and was well tolerated with a favorable safety profile. We are enrolling the Phase 3 multicenter, international, open label, and randomized (1:1) ARTEST registration clinical trial design to evaluate the efficacy and safety of enobosarm monotherapy versus physician’s choice of either exemestane everolimus or a SERM as the active comparator for the treatment of AR+ ER+ HER2- metastatic breast cancer in approximately 210 patients with AR nuclei staining ≥40% in their breast cancer tissue who had tumor progression on a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor.

Sabizabulin, Novel Oral Cytoskeleton Disruptor Agent, Monotherapy for the 3rd Line Treatment of AR+ER+HER2- Metastatic Breast Cancer with AR< 40% – Phase 2b Clinical Study.

We intend to conduct a Phase 2b clinical study of sabizabulin for the treatment of AR+ ER+ HER2- metastatic breast cancer in patients with an AR nuclei staining <40%. The Phase 2b clinical study will be an open label, multicenter, and randomized (1:1) study evaluating the efficacy and safety of sabizabulin 32mg monotherapy versus active comparator (exemestane ± everolimus or a SERM, physician’s choice) for the treatment of ER+ HER2- metastatic breast cancer in approximately 200 patients with AR nuclei staining <40% in their breast cancer tissue who had tumor progression on a nonsteroidal aromatase inhibitor, fulvestrant, and a CDK4/6 inhibitor. The Phase 2b study is expected to commence in calendar Q1 2022.

Enobosarm and Abemaciclib, CDK 4/6 Inhibitor, Combination Therapy for the 2nd Line Treatment of AR+ER+HER2- Metastatic Breast Cancer with AR ≥ 40% – Phase 3 ENABLAR-2 Clinical Study.

CDK 4/6 inhibitor and estrogen blocking agent combination has become first line therapy for patients with ER+HER2- advanced breast cancer. Unfortunately, almost all patients will develop resistance to CDK 4/6 inhibitors, and will eventually, have breast cancer progression. Based on positive Phase 2 clinical data and the preclinical data supporting the use of enobosarm in combination with a CDK 4/6 inhibitor in patients that are CDK 4/6 inhibitor and estrogen blocking agent resistant, we plan to conduct a Phase 3 multicenter, open label, randomized (1:1), active control clinical study, named ENABLAR-2 to evaluate the efficacy and safety of enobosarm plus abemaciclib combination therapy versus an alternative estrogen blocking agent (fulvestrant or an aromatase inhibitor) in subjects with AR+ ER+ HER2- metastatic breast cancer who have failed first line palbociclib (a CDK 4/6 inhibitor) plus an estrogen blocking agent (non-steroidal aromatase inhibitor or fulvestrant) and have an AR nuclei staining ≥ 40% in their breast cancer tissue. We plan to enroll approximately 186 subjects in this Phase 3 clinical study which is expected to commence during the first quarter of calendar year 2022.

Sabizabulin and Enobosarm Combination Therapy for AR+ Metastatic Triple Negative Breast Cancer Patients who have Progressed After Receiving at Least Two Systemic Chemotherapies – Phase 2 Clinical Study.

Sabizabulin is an oral, first-in-class, new chemical entity that targets and inhibits microtubules to disrupt the cytoskeleton. Sabizabulin is not a substrate for P-glycoprotein drug resistance protein. Over expression of P-glycoprotein is a common mechanism that results in taxane and chemotherapy resistance in metastatic triple negative breast cancer. Preclinical studies in human triple negative breast cancer grown in animal models demonstrate that sabizabulin significantly inhibits cancer proliferation, migration, metastases, and invasion of triple negative breast cancer tumors that have become resistant to paclitaxel (taxane). Furthermore, an enobosarm + pembrolizumab combination Phase 2 study in 18 heavily pretreated women with AR+ metastatic triple negative breast cancer demonstrated that enobosarm was well tolerated and resulted in promising preliminary efficacy of 25% clinical benefit rate (CR+PR+SD) at 16 weeks and objective tumor responses (1 CR and 1 PR). Thus, the combination of two oral agents, sabizabulin + enobosarm, may provide a new treatment option for women who have AR+ metastatic triple negative breast cancer. We intend to conduct a single arm, sabizabulin plus enobosarm combination therapy Phase 2 clinical study in approximately 111 women in calendar Q1 2022.

Companion Diagnostic AR Test
We have identified that patients who have greater than 40% androgen receptor nuclei staining in their breast cancer tissue are most likely to respond to enobosarm. Based on the recommendation of FDA to have a companion diagnostic test to determine the patient’s AR status, we are partnering with Roche/Ventana Diagnostics, a global oncology diagnostics company, who will develop and, if approved, commercialize a companion diagnostic AR test. The companion diagnostic test will be developed in parallel with the Phase 3 ARTEST clinical study.

Prostate Cancer Program

Sabizabulin, a Novel Oral Androgen Receptor Transport Disruptor, for the Treatment of Metastatic Castration and Androgen Receptor Targeting Agent Resistant Prostate Cancer – Phase 3 VERACITY Clinical Study – Enrolling.

Sabizabulin is a novel oral new chemical entity that targets microtubules in the cytoskeleton to disrupt androgen receptor transport. In June, the Company initiated the open label, randomized (2:1), multicenter Phase 3 VERACITY clinical study evaluating sabizabulin 32mg versus an alternative androgen receptor targeting agent for the treatment of chemotherapy naïve men with metastatic castration resistant prostate cancer who have failed at least one androgen receptor targeting agent. The primary endpoint is radiographic progression free survival. The Phase 3 VERACITY clinical study is expected to enroll approximately 245 patients from 45 clinical centers.

VERU-100, a Novel Proprietary Long-Acting Gonadotropin-Releasing Hormone (GnRH) Antagonist Peptide 3-Month Subcutaneous Depot Formulation, for Androgen Deprivation Therapy of Advanced Prostate Cancer – Phase 2 Clinical Study – Enrolling.

VERU-100 formulation is designed to address the current limitations of commercially available androgen deprivation therapy. Androgen deprivation therapy is currently the mainstay of advanced prostate cancer treatment and is used as a foundation of treatment throughout the course of the disease even as other endocrine, chemotherapy, or radiation treatments are added or stopped. Specifically, VERU-100 is a chronic, long-acting GnRH antagonist peptide administered as a small volume, three-month depot subcutaneous injection without a loading dose. VERU-100 immediately suppresses testosterone with no testosterone surge upon initial or repeated administration, a problem that occurs with currently approved luteinizing hormone-releasing hormone agonists used for androgen deprivation therapy. There are no GnRH antagonist depot injectable formulations commercially approved beyond a one-month injection. In June, the Company initiated the Phase 2 dose finding clinical study of VERU-100 androgen deprivation therapy for hormone sensitive advanced prostate cancer. The Phase 2 VERU-100 clinical study is expected to enroll approximately 35 patients. A Phase 3 registration clinical study has been agreed upon with FDA and will enroll approximately 100 men. The Phase 3 clinical study is anticipated to begin in 1H calendar 2022.

COVID-19 Program

Sabizabulin for the Treatment of Hospitalized COVID-19 Patients at High Risk for Acute Respiratory Distress Syndrome (ARDS) Phase 3 Clinical Study- Enrolling.

Sabizabulin has both broad anti-viral and anti-inflammatory activities which may serve a two-pronged approach to the treatment of COVID-19 virus infection and the subsequent debilitating inflammatory effects that lead to ARDS and death. In May, we initiated the Phase 3 clinical study which is a double-blind, multicenter, multinational, randomized (2:1), placebo-controlled study evaluating daily oral doses of 9mg sabizabulin for up to 21 days versus placebo in 300 hospitalized COVID-19 patients (200 subjects will be treated with sabizabulin and 100 subjects will receive standard of care) who are at high risk for ARDS. The primary efficacy endpoint will be proportion of patients that die on study up to Day 60. Secondary endpoints will include the proportion of patients without respiratory failure, days in ICU, WHO Ordinal Scale for Clinical Improvement change from baseline, days on mechanical ventilations, days in the hospital, and viral load. The study is being conducted in the US, Brazil, Argentina, Mexico, Colombia and Bulgaria.

Sexual Health Division

ENTADFI (Tadalafil 5mg and Finasteride 5mg Capsule) for the Treatment of Benign Prostatic Hyperplasia (BPH) – PDUFA Date December 2021.

ENTADFI (tadalafil 5mg and finasteride 5mg combination capsule) was developed to treat urinary tract symptoms caused by BPH without adverse sexual side effects. The co-administration of tadalafil and finasteride has been shown to be more effective for the treatment of BPH than finasteride alone without causing erectile dysfunction. The PDUFA date is scheduled for December 2021. If approved, ENTADFI is expected to be marketed and distributed by our own "direct to patient" telemedicine and telepharmacy platform. We have also partnered with GoodRx, America’s digital resource for healthcare, to reach their almost 20 million monthly visitors, which include both consumers and healthcare providers, and offer a unique cash price to ensure our treatment is more affordable and accessible. We will augment our marketing and sales efforts by seeking partners in the US and ex-US. We expect to begin commercialization in the first half of calendar year 2022.

Event Details
Interested parties may access the call by dialing 1-800-341-1602 from the U.S. or 1-412-902-6706 from outside the U.S. and asking to be joined into the Veru Inc. call. The call will also be available through a live, listen-only audio broadcast via the Internet at www.verupharma.com. Listeners are encouraged to visit the website at least 10 minutes prior to the start of the scheduled presentation to register, download and install any necessary software. A playback of the call will be archived and accessible on the same website for at least three months. A telephonic replay of the conference call will be available, beginning the same day at approximately 12 p.m. (noon) ET by dialing 1-877-344-7529 for U.S. callers, or 1-412-317-0088 from outside the U.S., passcode 10161217, for one week.

Surface Oncology to Present New Clinical Data from Ongoing SRF617 Phase 1 Trial at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO) 2021

On December 2, 2021 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported that a poster presentation sharing new clinical data from the ongoing SRF617 Phase 1 trial will be presented at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO) 2021, to be held virtually from December 8 to 11, 2021 (Press release, Surface Oncology, DEC 2, 2021, View Source [SID1234596399]).

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The poster includes new data from the ongoing Phase 1 study of SRF617, an antibody targeting CD39, as both a monotherapy and in combination, in patients with advanced solid tumors. The full poster will be placed on Surface Oncology’s website following the presentation.

Details of Surface’s ESMO (Free ESMO Whitepaper)-IO poster presentation:

Title: First-in-human phase 1 trial of SRF617, a potent inhibitor of CD39 activity, as monotherapy or in combination, in patients with advanced solid tumors
Poster Number: 135P
Lead Author: Amita Patnaik, M.D.
Presentation Date and Time: On-demand e-Poster will be available on December 6, 2021 at 12:00 CET (6:00 a.m. ET)

Karyopharm Completes Patient Recruitment in Phase 3 SIENDO Study of Selinexor in Patients with Endometrial Cancer

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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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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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.

SQZ Biotechnologies Lead Cell Therapy Candidate Generated Monotherapy Clinical Response Correlated with Substantial CD8 T Cell Tumor Infiltration in HPV+ Solid Tumor at Highest Dose

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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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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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.