On November 23, 2020 Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, reported financial results and business highlights for the fourth quarter and full year fiscal 2020 ended September 30, 2020 (Press release, Twist Bioscience, NOV 23, 2020, View Source [SID1234571596]).

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"We ended our fiscal year with record revenue and orders against the backdrop of a global pandemic and significant uncertainty," said Emily M. Leproust, Ph.D., CEO and co-founder of Twist Bioscience. "While we are proud of the new products we introduced to aid in the fight against COVID-19, which complemented our revenue, it was our core synthetic biology and next-generation sequencing (NGS) product lines that drove our overarching success.

"We have aggressive plans for growth and expansion in fiscal 2021 and beyond, continuing to build our foundation for sustained success across synthetic biology, NGS, biopharma and DNA data storage."

FISCAL 2020 FINANCIAL RESULTS

Orders: Total orders received for fiscal 2020 were $116.7 million compared to $70.0 million for fiscal 2019.
Revenue: Total revenues were $90.1 million for fiscal 2020 compared to $54.4 million for fiscal 2019.
Cost of Revenues: Cost of revenues for fiscal 2020 was $61.4 million compared to $47.4 million for fiscal 2019.
Research and Development Expenses: Research and development expenses for fiscal 2020 were $43.0 million compared to $35.7 million for fiscal 2019.
Selling, General and Administrative Expenses: Selling, general and administrative expenses for fiscal 2020 were $103.3 million compared to $80.1 million for fiscal 2019.
Net Loss: Net loss for fiscal 2020 was $139.9 million, or $3.57 per share, compared to $107.7 million, or $3.92 per share, for fiscal 2019.
Cash Position: As of September 30, 2020, the company had $290.0 million in cash, cash equivalents and short term investments.
FISCAL 2020 FOURTH QUARTER FINANCIAL RESULTS

Orders: Total orders received for the fourth quarter of fiscal 2020 were $42.7 million, compared to $20.0 million for the same period of fiscal 2019.
Revenue: Total revenues were $32.4 million for the fourth quarter of fiscal 2020 compared to $15.7 million for the same period of fiscal 2019.
Cost of Revenues: Cost of revenues for the fourth quarter of fiscal 2020 was $17.6 million compared to $12.4 million for the same period of fiscal 2019.
Research and Development Expenses: Research and development expenses for the fourth quarter of fiscal 2020 were $11.7 million compared to $10.5 million for the same period of fiscal 2019.
Selling, General and Administrative Expenses: Selling, general and administrative expenses for the fourth quarter of fiscal 2020 were $27.2 million compared to $24.4 million for the same period of fiscal 2019.
Net Loss: Net loss for the fourth quarter of fiscal 2020 was $24.3 million, or $0.54 per share, compared to $31.2 million, or $0.96 per share, for the fourth quarter of fiscal 2019.
"Over the last year, we delivered on revenue, orders, margin and product pipeline in a very challenging environment," commented Jim Thorburn, CFO of Twist. "We have a strong balance sheet and momentum moving into fiscal 2021, and look forward to an exciting year ahead."

Fiscal Fourth Quarter 2020 and Recent Highlights

Shipped products to approximately 2,200 customers in fiscal 2020, versus approximately 1,300 in fiscal 2019.
Presented data on our Twist Custom Target Capture Panel, Fast Hybridization Enrichment System and our Target Enrichment for Infectious Disease at the American Society of Human Genetics 2020 Annual Meeting.
Announced broad strategic partnership with Neogene Therapeutics, Inc. to leverage Neogene’s proprietary expertise in targeting tumor neo-antigens, mutated proteins found in cancer cells due to cancer-associated DNA mutations, together with Twist’s DNA synthesis platform and product lines to develop personalized chimeric antigen receptor (CAR) T cell therapies and T cell receptor (TCR) therapies for patients with cancer.
Reported preclinical data demonstrating the potent neutralizing effects of multiple potential therapeutic antibodies identified by Twist Biopharma, both Immunoglobulin G (IgG) antibodies and substantially smaller single domain VHH "nanobodies," against SARS-CoV-2, the virus that causes COVID-19. These neutralizing effects were found to be comparable to or better than those seen with antibody candidates derived from patients who had recovered from COVID-19. The data were collected from studies conducted by Saint Louis University and independently verified by scientists at Colorado State University.
Achieved significant milestones on our DNA data storage roadmap to miniaturize the silicon platform technology down to 150 nanometer pitch or less. Twist is now consistently able to synthesize DNA using five-micron devices at a 10 micron pitch. In addition, we have fabricated our next R&D-stage silicon chip with 300 nanometer devices on a one-micron pitch chip.
Formed the DNA Data Storage Alliance with leading technology and synthetic biology companies to create a comprehensive industry roadmap designed to help the industry achieve interoperability between solutions and help establish the foundations for a cost-effective commercial archival storage ecosystem for the explosive growth of digital data.
New Netflix Original Series ’Biohackers’ stored in Twist’s synthetic DNA.
Fiscal 2021 Financial Guidance

The following statements are based on Twist’s current expectations for fiscal 2021. The following statements are forward-looking, and actual results could differ materially depending on market conditions and the factors set forth under "Forward-Looking Statements" below. Twist does not plan to update, nor does it undertake any obligation to update, this outlook in the future.

For the full fiscal year 2021, Twist provided the following financial guidance:

Revenue expected in the range of $110 million to $118 million
Revenue from Ginkgo Bioworks expected to be approximately $11 to $12 million
Synbio revenue excluding Ginkgo Bioworks is expected to be in the range of $41 to $44 million
NGS revenue is estimated to be in the range of $54 to $58 million
Biopharma revenue is estimated to be approximately $4 million
Gross margin is expected to be approximately 32% for fiscal 2021
Operating expenses including R&D and SG&A are expected to be $174 million for the year
Net loss expected in the range of $136 million to $141 million to reflect our increased investments in our commercial organization and research and development activities
R&D is expected to be approximately $60 million
Stock-based compensation is expected to be approximately $20 million
Depreciation is expected to be $7 million
Capital expenditures are expected to be $30 million, including expansion into "Factory of the Future"
Fiscal 2021 First Quarter Financial Guidance

For the first quarter of fiscal 2021, Twist provided the following financial guidance:

Revenue expected in the range of $25 million to $26 million
COVID-19 Considerations

During the three months ended September 30, 2020, financial results of the Company were not significantly affected by the COVID-19 outbreak. However, the extent to which the COVID-19 outbreak affects Twist’s future financial results and operations is subject to a high degree of uncertainty and will depend on future developments, including the duration, spread and treatment of the outbreak domestically and abroad.

Conference Call Information

The company plans to hold a conference call and live audio webcast for analysts and investors today at 8:00 a.m. Eastern Time to discuss its financial results and provide an update on the company’s business. The call can be accessed by dialing (866) 688-0947 (domestic) or (409) 217-8781 (international) and refer to the conference ID 2947139. A telephonic replay of the conference call will be available beginning approximately four hours after the call through November 30, 2020 and may be accessed by dialing (855) 859-2056 (domestic) or (404) 537-3406 (international). The replay conference ID is 2947139. The webcast replay will be available for two weeks.

Given the circumstances globally, it is recommended to dial-in at most 15 to 20 minutes prior to the call start to reduce waiting times. If a participant will be listen-only, they are encouraged to listen via the webcast on Twist’s investor page.

On November 23, 2020 Immunocore (the "Company"), a late-stage biotechnology company pioneering the development of a novel class of TCR bispecific immunotherapies designed to treat a broad range of diseases, including cancer, infectious and autoimmune, reported that its Phase 3 IMCgp100-202 clinical trial of tebentafusp (IMCgp100) vs. investigator choice in metastatic uveal melanoma (mUM) has met the pre-defined boundaries for statistical significance of the primary endpoint of Overall Survival (OS) in its first pre-planned interim analysis conducted by the independent data monitoring committee (Press release, Immunocore, NOV 23, 2020, View Source [SID1234571630]). The OS Hazard Ratio (HR) in the intent-to-treat population favored tebentafusp, HR=0.51 (95% CI: 0.36, 0.71); p< 0.0001, over investigator’s choice (82% pembrolizumab; 12% ipilimumab; 6% dacarbazine). Although not yet mature, the Kaplan-Meier estimates suggest a 1-year OS rate of approximately 73% vs 58%, respectively. The efficacy data confirm the promising OS observed in the phase 2 study IMCgp100-102 in previously treated mUM which will be presented next month at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Virtual Congress 2020.

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Bahija Jallal, Chief Executive Officer of Immunocore said: "A positive survival benefit for tebentafusp represents a major step towards bringing a potential new treatment for cancer patients with a high unmet need. If approved, tebentafusp would be the first new therapy to improve overall survival in 40 years and to be specifically indicated for metastatic uveal melanoma, a disease with poor survival and where new therapies are urgently needed. We look forward to sharing these data with the medical community and Health Authorities in the near future."

Tebentafusp is a novel bispecific protein comprised of a soluble T cell receptor fused to an anti-CD3 immune-effector domain. It is engineered to specifically target gp100, a lineage antigen expressed in melanocytes and melanoma, and is the first molecule developed using Immunocore’s ImmTAC technology platform designed to redirect and activate T cells to recognize and kill tumor cells. Tebentafusp has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) and has previously been granted orphan drug designation for uveal melanoma by the FDA and Promising Innovative Medicine designation under UK Early Access to Medicines Scheme.

"To our knowledge, this is the first survival benefit for any TCR therapeutic and for any bispecific in a solid tumor. The survival benefit observed in a randomized trial against checkpoint inhibitors validates our ImmTAC platform as we expand to study other cancers with high unmet need," said David Berman, Head of R&D, "Uveal melanoma has one of the lowest tumor mutational burdens (TMB) and these results suggest our ImmTAC platform should be evaluated in tumors with low or high TMB status."

The Phase 3 IMCgp100-202 clinical trial is designed to evaluate the OS of tebentafusp compared to investigator’s choice (either dacarbazine, ipilimumab or pembrolizumab) in patients with previously untreatedmUM. 378 patients were randomized in a 2:1 ratio to either tebentafusp or investigator’s choice. Final results from IMCgp100-202 are expected to be presented at an upcoming scientific conference and to be submitted for publication in a peer-reviewed journal.

On November 22, 2020, Baudax Bio, Inc., (the "Company"), reported that it entered into a Securities Purchase Agreement (the "Purchase Agreement") with an institutional investor named therein (the "Purchaser"), pursuant to which the Company agreed to issue and sell, in a registered direct offering (the "Offering"), 2,850,000 shares (the "Shares") of the Company’s common stock, par value $0.01 per share (the "Common Stock") and warrants exercisable for an aggregate of 10,126,583 shares of Common Stock (the "Series A Warrants") at a combined offering price of $1.185 per share (Filing, 8-K, Baudax Bio, NOV 22, 2020, View Source [SID1234572278]). The Series A Warrants have an exercise price of $1.20 per share. Each Series A Warrant is exercisable for one share of Common Stock and will be immediately exercisable and will expire five years from the issuance date.

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The Company also offered and sold to the Purchaser pre-funded warrants to purchase an aggregate of 7,276,583 shares of Common Stock (the "Series B Warrants" and, together with the Shares and the Series A Warrants, the "Securities"), in lieu of shares of Common Stock at the Purchaser’s election. Each Series B Warrant is exercisable for one share of our Common Stock. The purchase price of each Series B Warrant is $1.175, and the exercise price of each pre-funded Series B Warrant is $0.01 per share. The Series B Warrants are immediately exercisable and may be exercised at any time until all of the Series B Warrants are exercised in full.

A holder (together with its affiliates) may not exercise any portion of such holder’s Series A Warrants or Series B Warrants to the extent that the holder would own more than 4.99% (or 9.99%, at the holder’s election) of the Company’s outstanding Common Stock immediately after exercise, except that upon notice from the holder to the Company, the holder may decrease or increase the limitation of ownership of outstanding stock after exercising the holder’s Series A Warrants or Series B Warrants up to 9.99% of the number of shares of the Company’s Common Stock outstanding immediately after giving effect to the exercise, as such percentage ownership is determined in accordance with the terms of the Series A Warrants and Series B Warrants, provided that any increase in such limitation shall not be effective until 61 days following notice to the Company.

The Purchase Agreement contains customary representations and warranties and agreements of the Company and the Purchaser and customary indemnification rights and obligations of the parties. The closing of the Offering is expected to occur on November 25, 2020. The Company is expected to receive gross proceeds of approximately $11.9 million in connection with the Offering, before deducting placement agent fees and related offering expenses.

As compensation to H.C. Wainwright & Co., LLC (the "Placement Agent") as placement agent in connection with the Offering, the Company agreed to pay to the Placement Agent a cash fee of 6.0% of the aggregate gross proceeds raised in the Offering, plus a management fee equal to 1.0% of the gross proceeds raised in the Offering and reimbursement of certain expenses and legal fees. The Company will also issue to designees of the Placement Agent warrants to purchase up to 6.0% of the aggregate number of shares of Common Stock sold in the transactions, or warrants to purchase up to 607,595 shares of Common Stock (the "Placement Agent Warrants"). The Placement Agent Warrants have substantially the same terms as the Series A Warrants, except that the Placement Agent Warrants have an exercise price equal to 125% of the offering price per share (or $1.48125 per share).

The foregoing summaries of the Purchase Agreement, the Series A Warrants, Series B Warrants and the Placement Agent Warrants do not purport to be complete and are subject to, and qualified in their entirety by, the forms of such documents attached as Exhibits 10.1, 4.1, 4.2 and 4.3, respectively, to this Current Report on Form 8-K (the "Report"), which are incorporated herein by reference.

The Securities in the Offering and the Placement Agent Warrants were offered by the Company pursuant to a registration statement on Form S-3 (File No. 333-243488), which was filed with the Securities and Exchange Commission on August 10, 2020 and was declared effective by the Commission on October 2, 2020 (the "Registration Statement"). A copy of the opinion of Troutman Pepper Hamilton Sanders LLP relating to the legality of the issuance and sale of the Securities in the Offering is attached as Exhibit 5.1 hereto. This Report shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

On November 20, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the results of the Phase 3 ORIENT-32 study were released in a late-breaking proffered oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Asia ("ESMO Asia") Virtual Congress 2020 (Press release, Innovent Biologics, NOV 22, 2020, View Source [SID1234571528]).

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ORIENT-32 is the first randomized Phase 3 study reporting the efficacy and safety of an anti-PD-1 antibody-based combination therapy versus sorafenib as the first-line treatment in patients with advanced unresectable hepatocellular carcinoma (HCC). A total of 571 patients were enrolled in the trial. Based on an interim analysis conducted by the study’s Independent Data Monitoring Committee (IDMC), TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) demonstrated significantly improved overall survival (OS) and Independent Radiographic Review Committee (IRRC) progression-free survival (PFS) versus sorafenib. Compared to sorafenib, TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) demonstrated a 43.1% decreased risk of all-cause mortality (HR 0.569, 95%CI: 0.431-0.751, P<0.0001); the median OS was not reached in the TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) arm versus 10.4 months in the sorafenib arm. TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) also demonstrated 43.5% decreased risk of progression as assessed by IRRC (HR 0.565 95%CI: 0.455-0.701, P<0.0001); median PFS was 4.6 months in the TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) arm versus 2.8 months in the sorafenib arm.

The significantly improved OS and PFS benefits brought by TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) over sorafenib were generally consistent across all subgroups. The combination regimen showed an acceptable safety profile with no new safety signals. With these results, TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) could potentially provide a new option for the first-line treatment of patients with advanced HCC.

Dr. Hui Zhou, Vice President and Head of Oncology Strategy and Medical Sciences of Innovent, stated: "In China, HCC is the fourth most common malignancy with the second highest mortality rate. More than half of new and fatal cases of HCC in the world occur in China every year. Despite the challenges and impact from the COVID-19 pandemic, the ORIENT-32 study was carried out smoothly and successfully under the joint efforts of all investigators and patients with their families. We are very pleased to see that the ORIENT-32 study demonstrated significant prolongation of OS and PFS in advanced HCC patients in China. With these encouraging results，we will apply to the National Medical Products Administration for the new drug application of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection). We look forward to this potentially becoming a new treatment regimen that could help more patients with HCC to live longer without their disease worsening."

About ORIENT-32 Trial

ORIENT-32 is a Phase 3 randomized, open-label，multi-center study to evaluate the efficacy and safety of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) compared to sorafenib in the first-line treatment of patients with advanced hepatocellular carcinoma（ClinicalTrials.gov, NCT 03794440）. The primary endpoints of the trial are overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.

Enrolled patients were randomly assigned 2:1 to receive TYVYT (sintilimab injection) combination with BYVASDA (bevacizumab biosimilar injection) or sorafenib, until disease progression, unacceptable toxicity, withdrawal of consent, death, or other reasons stated in the protocol, whichever occurs first.

About Hepatocellular Carcinoma (HCC)

Primary liver cancer（PLC）is a common malignancy of the digestive system worldwide, among which about half new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), accounting for 85 to 90 percent, and a small number of cases of intrahepatic cholangiocarcinoma（ICC） and HCC-ICC mixed liver cancer. In China, HCC is primarily caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.

About TYVYT (Sintilimab Injection)

TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Lilly, has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy, and included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT (sintilimab injection) is the only PD-1 inhibitor included in the new Catalogue of the National Reimbursement Drug List (NRDL). In April 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy as first-line therapy for the treatment of patients with nonsquamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT (sintilimab injection) monotherapy met the primary endpoint of overall survival in the Phase 2 ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma. In August 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with GEMZAR (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC. In September 2020, TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as a first-line treatment in advanced hepatocellular carcinoma met the predefined primary endpoints of overall survival and progression-free survival in an interim analysis of the Phase 3 ORIENT-32 study.

TYVYT (sintilimab injection) is a fully human immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies for TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. This includes global clinical research studies on TYVYT (sintilimab injection).

About BYVASDA (Bevacizumab Biosimilar Injection)

BYVASDA is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF selectively with high affinity and blocks its binding to VEGF receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since the launch of bevacizumab, it has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab have been well recognized worldwide.

On November 20, 2020 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported it will present positive results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral XPOVIO (selinexor) versus matching placebo in patients with liposarcoma at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020) (Press release, Karyopharm, NOV 20, 2020, View Source [SID1234571490]). As previously reported, the SEAL study met its primary endpoint of a statistically significant increase in median progression-free survival (PFS) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies.

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"Dedifferentiated liposarcoma is a particularly aggressive cancer that arises in the body’s fat tissue and is typically associated with high rates of metastatic recurrence and mortality. Unfortunately, there are few effective treatment options available for patients with advanced disease," said Mrinal M. Gounder, MD, Attending Physician, Sarcoma Service and Developmental Therapeutics Service, Memorial Sloan Kettering Cancer Center, and lead investigator of the SEAL study. "The data presented at CTOS 2020 demonstrated that patients treated with XPOVIO experienced a statistically significant improvement in median PFS compared to placebo in patients with at least two prior therapies. Extending PFS is an important clinical goal for these patients because the rapid progression of this disease often translates into early mortality."

"We are delighted to share these significant results from the Phase 3 portion of the SEAL study, the first, late-stage clinical data for XPOVIO in a solid tumor indication," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "We believe these data strongly support our goal of developing twice-weekly XPOVIO as an effective, convenient, novel oral therapy that can extend PFS for patients with advanced unresectable dedifferentiated liposarcoma. We are especially excited by these data because XPOVIO is the first oral therapy to show activity in patients with previously treated liposarcoma. We look forward to submitting a New Drug Application to the U.S. Food and Drug Administration (FDA) during the first quarter of 2021, requesting approval of XPOVIO to treat the patient population studied in SEAL. If approved, XPOVIO would represent the first oral, non-chemotherapy agent available for patients with dedifferentiated liposarcoma."

Results from the Phase 3 Portion of the Phase2/3 SEAL Study

The median PFS in the XPOVIO arm of the Phase 3 portion of the SEAL study was 2.83 months compared to 2.07 months in the placebo arm (hazard ratio (HR)=0.70; p=0.023). These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The estimated 6-month PFS survival probability was 23.9% on the selinexor arm compared to 13.9% on placebo. Additionally, the 12-month PFS survival probability was 8.4% on the selinexor arm compared to 2% on the placebo arm. Finally, 7.5% of patients on the selinexor arm had a 15% or greater reduction in their disease burden as measured by target lesion size while none of the patients on the placebo arm achieved this level of reduction. The trial allowed patients on placebo with objective progression to cross over to the XPOVIO treatment arm. The median overall survival for patients who received XPOVIO was 9.99 months compared to 9.07 months for patients who never crossed over to the XPOVIO treatment arm (HR=0.69; p=0.122).

The most common treatment-related adverse events (AEs) were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most AEs were manageable with dose modifications and/or standard supportive care. The most common non-hematologic treatment-related AEs were nausea (81%), decreased appetite (60%), fatigue (51%), and vomiting (49%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 treatment-related AEs were anemia (19%), hyponatremia (11%), thrombocytopenia (10%) and asthenia (10%).

XPOVIO is currently approved by the FDA as a treatment for patients with relapsed or refractory multiple myeloma and relapsed or refractory diffuse large B-cell lymphoma (DLBCL). XPOVIO is currently the only XPO1 inhibitor approved by the FDA and has been extensively tested in clinical trials across numerous cancer indications worldwide since 2012. Karyopharm has also submitted a supplemental New Drug Application (sNDA) for XPOVIO that is currently under review by the FDA for the expansion of XPOVIO’s label to include XPOVIO as a treatment for patients with multiple myeloma after at least one prior line of therapy. The sNDA has been assigned an action date by the FDA of March 19, 2021 under the Prescription Drug User Fee Act. The full Prescribing Information for XPOVIO is available at www.XPOVIO.com.

Details for the oral presentation at CTOS 2020 are as follows:

Title: A Phase 2/3, Randomized, Double-Blind, Cross-Over Study of Selinexor Versus Placebo in Advanced Unresectable Dedifferentiated Liposarcoma (DDLS)
Presenter: Mrinal Gounder, MD, Memorial Sloan Kettering Cancer Center
Paper #: 20
Session: 7. Liposarcoma
Date and Time: Friday, November 20, 2020, 10:30 a.m. to 11:30 a.m. ET

Conference Call Information

Karyopharm will host a conference call today, Friday, November 20, 2020, at 12:00 p.m. Eastern Time, to discuss the results from the SEAL study. The call will feature Dr. Gounder and another recognized sarcoma expert Sant P. Chawla, MD, FRACP, Director of the Sarcoma Oncology Center, Santa Monica, CA, along with members of the Karyopharm executive leadership team. To access the conference call, please dial (877) 870-4263 (local) or (412) 317-0790 (international) at least 10 minutes prior to the start time and ask to be joined into the Karyopharm Therapeutics call. A live audio webcast of the call, along with slides, will be available under "Events & Presentations" in the Investor section of the Company’s website, View Source An archived webcast will be available on the Company’s website approximately two hours after the event.

About the SEAL Study

SEAL (Selinexor in Advanced Liposarcoma) is a Phase 2/3, randomized, double blind, placebo controlled, multicenter study (NCT02606461) designed to evaluate the efficacy and safety of twice-weekly, 60mg fixed dose of XPOVIO (selinexor) in patients with advanced unresectable dedifferentiated liposarcoma following at least two prior therapies. The Phase 2 portion of the study enrolled approximately 57 patients (1:1 randomization) and the Phase 3 portion enrolled approximately 285 patients (2:1 randomization). Patients on the placebo arm with confirmed progressive disease were permitted to cross over to the XPOVIO treatment arm. The primary endpoint of the study is PFS.

About Liposarcoma

Liposarcoma is a rare type of cancer that occurs in the fat cells in the body, most often in the muscles of the limbs or abdomen. Dedifferentiated liposarcoma (DDLS) is a high grade type of liposarcoma that grows more aggressively than a low grade, well differentiated liposarcoma and is associated with poorer prognosis.1 Liposarcoma accounts for approximately 20% of all soft tissue sarcomas2. In liposarcoma, the risk of recurrence and metastasis increases with higher grade disease.3

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 or 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. Karyopharm has also submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) with a request for conditional approval of selinexor in this same RRMM indication. Karyopharm’s supplemental New Drug Application (sNDA) requesting an expansion of its current indication to include the treatment for patients with multiple myeloma after at least one prior line of therapy has been accepted for filing by the FDA. 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), in liposarcoma (SEAL) 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.