On March 16, 2022 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company targeting virus-associated malignancies, reported financial results for the fourth quarter and full year 2021 and provided an update on recent corporate activities (Press release, Sunesis, MAR 16, 2022, View Source [SID1234610176]).

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"In 2021, we achieved key corporate and clinical milestones that we believe positioned us for an exciting year ahead," said Ivor Royston, M.D., President and Chief Executive Officer of Viracta. "We entered the public market while simultaneously completing a successful equity financing, and initiated two clinical studies of our all-oral combination therapy, Nana-val. These included our pivotal NAVAL-1 trial in EBV-positive relapsed/refractory lymphoma and our Phase 1b/2 trial in advanced EBV-positive solid tumors. In addition, we ended the year by presenting final data from Nana-val’s Phase 1b/2 EBV-positive lymphoma trial in an oral presentation at ASH (Free ASH Whitepaper) 2021, which showed complete responses in a heavily pre-treated patient population in need of a new therapeutic option."

Dr. Royston continued, "In the year ahead, we anticipate several important advancements and milestones in our clinical programs, including meaningful progress in NAVAL-1, and a preliminary data readout from our ongoing Phase 1b/2 trial in solid tumors. Should we see early efficacy signals for Nana-val in solid tumors, as we did in the Phase 1b/2 EBV-positive lymphoma trial, it could serve as initial support for our pursuit of a tissue agnostic approach to EBV-associated malignancies and expand our addressable patient population. With a cash runway into mid-2024, we are well capitalized to execute on these milestones and our broader corporate strategy."

Fourth Quarter 2021 and Recent Highlights
Clinical

Presented final results from the Phase 1b/2 trial of Nana-val (nanatinostat and valganciclovir) in relapsed/refractory (R/R) EBV+ lymphoma, in an oral presentation at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Data featured in the presentation were from 55 patients with a median of two prior therapies. 75% (41/55) of patients were refractory to their last therapy, and 96% (53/55) had exhausted all standard therapies (per Investigator).
Efficacy data in evaluable patient (n=43):

Across all lymphoma subtypes: overall response rate (ORR) = 40% (17/43); complete response (CR) = 19% (8/43)
T/NK- non-Hodgkin lymphoma: ORR = 60% (9/15); CR = 27% (4/15)
Extranodal NK/T-Cell Lymphoma (ENKTL): ORR = 63% (5/8); CR = 13% (1/8)
Peripheral T-cell lymphoma (PTCL)/ Angioimmunoblastic T-cell lymphoma (AITL): ORR = 67% (4/6); CR = 50% (3/6)
Diffuse large B cell lymphoma (DLBCL): ORR = 67% (4/6); CR = 33% (2/6); Both DLBCL complete responses were in patients refractory to first line R-CHOP
Immunodeficiency-associated lymphoproliferative disorders (IA-LPD): ORR = 50% (3/6); CR = 33% (2/6)
Median duration of response was 10.4 months
Nana-val was generally well tolerated with reversible low-grade toxicities. The most commonly reported treatment emergent adverse events were reversible cytopenias, low grade creatinine elevations, and gastrointestinal symptoms.

Continued enrollment into, and global expansion of, pivotal NAVAL-1 trial of Nana-val for the treatment of R/R EBV+ lymphoma. NAVAL-1 employs a Simon two-stage design where patients are initially enrolled into six cohorts based on lymphoma subtype in Stage 1. If a pre-specified activity threshold is reached, additional patients will be enrolled in Stage 2. Lymphoma subtypes demonstrating promising activity in Stage 2 may be further expanded. If successful, the Company believes NAVAL-1 could potentially support multiple new drug application (NDA) filings across various EBV+ lymphoma subtypes. The Company anticipates providing an update on the initial cohort(s) that expand into Stage 2 in the second half of 2022.
Dosed first patient in the Phase 1b/2 trial of Nana-val for the treatment of EBV+ recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) and other EBV+ solid tumors. The Phase 1b dose escalation portion of the study will evaluate safety and determine the recommended Phase 2 dose (RP2D) of Nana-val in patients with EBV+ R/M NPC. In Phase 2, up to 60 patients with EBV+ R/M NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to evaluate safety and preliminary efficacy. Additionally, patients with other EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort. Viracta anticipates reporting preliminary Phase 1b safety and efficacy data from the trial in the second half of 2022.
Received orphan drug designation (ODD) from U.S. Food and Drug Administration (FDA) for Nana-val for the treatment of EBV+ Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS). This represents the first ODD for EBV+ DLBCL, NOS granted by the FDA, and the fourth ODD granted for Nana-val overall. The FDA previously granted ODD to Nana-val for the treatment of T-cell lymphoma, post-transplant lymphoproliferative disorder and plasmablastic lymphoma.
Preclinical

Presented preclinical data on vecabrutinib, a reversible inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK), at the 2021 ASH (Free ASH Whitepaper) Annual Meeting. Two presentations were featured, oral and poster, with data that demonstrate the capacity of vecabrutinib to modulate immune responses. Data featured in the oral presentation showed vecabrutinib enhancing the efficacy of chimeric antigen receptor (CAR) T-cells in a murine mantle cell lymphoma model. Vecabrutinib also inhibited secretion of pro-inflammatory cytokines known to cause toxicities associated with CAR T-cell therapy, an observation that was consistent with data from a prior Phase 1 clinical trial evaluating vecabrutinib as a treatment for patients with B-cell malignancies. Data featured in the poster presentation show vecabrutinib significantly reducing signs of sclerodermatous chronic graft versus host disease (cGVHD), including skin irritation, redness, alopecia, and diarrhea, via modulation of pathogenetic B- and T-cell subsets in a murine disease model.
Corporate

Announced addition to the Nasdaq Biotechnology Index (NBI). The NBI is designed to track the performance of a set of securities listed on The Nasdaq Stock Market (Nasdaq) that are classified as either biotechnology or pharmaceutical according to the Industry Classification Benchmark (ICB). The NBI is re-ranked each year and is calculated under a modified capitalization-weighted methodology. Additionally, the NBI forms the basis for a number of Exchange Traded Funds (ETFs).
Secured expanded $50 million credit facility from Silicon Valley Bank (SVB) and Oxford Finance. The credit facility replaces Viracta’s prior $15 million loan and security agreement with SVB and provides the Company with the option to obtain additional non-dilutive funding at a single-digit cost of capital. Through this expanded credit facility, the Company’s existing $5.0 million debt balance was refinanced. The remaining $45.0 million is available to the Company, which is under no obligation to draw funds in the future.
Anticipated 2022 Milestones
Provide preliminary Phase 1b safety and efficacy data from the Phase 1b/2 trial in advanced EBV+ solid tumors: 2H 2022
Update on NAVAL-1 cohort(s) progressing from Stage 1 to Stage 2: 2H 2022
Fourth Quarter and Full Year 2021 Financial Results
Cash Position – Cash and cash equivalents totaled approximately $103.6 million as of December 31, 2021, which Viracta expects will be sufficient to fund its operations into mid-2024, excluding any additional borrowings under the $50.0 million credit facility.
Research and development expenses – Research and development expenses were approximately $7.3 million and $3.6 million for the fourth quarters ended 2021 and 2020, respectively. Research and development expenses were approximately $23.9 million and $13.5 million for years ended December 31, 2021, and December 31, 2020, respectively. The increase in research and development expenses was primarily due to increases in costs incurred to support the initiation of the NAVAL-1 and solid tumor trials as well as an increase in headcount and non-cash share-based compensation.
Purchased and acquired in-process research and development – Purchased and acquired in-process research and development expenses were $88.5 million for the year ended December 31, 2021. The expenses were related to the $4.0 million payment associated with the termination of the collaboration and license agreement with Shenzhen Salubris Pharmaceutical Co. Ltd. and non-cash and non-recurring costs of $84.5 million related to the write-off of in-process research and development acquired in the merger with Sunesis Pharmaceuticals.
General and administrative expenses – General and administrative expenses were approximately $4.0 million and $2.6 million for the fourth quarters ended 2021 and 2020, respectively. General and administrative expenses were approximately $15.4 million and $5.3 million for the years ended December 31, 2021, and December 31, 2020, respectively. The increase was largely due to significant and non-recurring costs associated with the merger, in addition to incremental costs associated with being a publicly traded company, including legal fees, audit fees, consulting expenses, filing fees and increased directors’ and officers’ insurance costs, in addition to an increase in non-cash share-based compensation.
Gain on Royalty Purchase Agreement – Gain on Royalty Purchase Agreement the year ended December 31, 2021, was associated with upfront proceeds of $13.5 million received in connection with the multi-license milestone and royalty monetization transaction with XOMA Corporation in March 2021.
Adjusted loss from operations – Adjusted loss from operations for the year ended December 31, 2021, excluding the non-recurring operating expenses associated with the write-off of in-process research and development acquired in the merger and the termination agreement with Salubris Pharmaceutical Co. Ltd. (a non-GAAP measure) was $25.8 million, compared to a loss from operations of $114.3 million. There is not a comparative adjustment to loss from operations for the same period in 2020.
Net loss – Net loss was approximately $11.4 million, or $0.31 per share (basic and diluted), and approximately $6.3 million, or $13.31 per share (basic and diluted), for the fourth quarters ended 2021 and 2020, respectively. Net loss was approximately $114.8 million, or $3.60 per share (basic and diluted) for the year ended December 31, 2021, compared to a net loss of approximately $19.0 million, or $58.56 per share (basic and diluted) for the year ended December 31, 2020.
About Nana-Val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which is key to inducing viral genes that are epigenetically silenced in EBV-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-Val, in various subtypes of EBV-associated malignancies. Ongoing trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed/refractory EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 trial in patients with EBV+ recurrent or metastatic nasopharyngeal carcinoma and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 95% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of lymphatic cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden and is also associated with a variety of solid tumors, including nasopharyngeal carcinoma and gastric cancer.

About Vecabrutinib
Vecabrutinib is a well-tolerated, selective, reversible, non-covalent inhibitor of Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK). Vecabrutinib is being studied as a potential enhancer of efficacy and safety of CAR T-cell therapy.

On March 16, 2022 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported that the U.S. Food and Drug Administration (FDA) has cleared the Company’s Investigational New Drug (IND) application for SON-1010, a proprietary version of Interleukin 12 (IL-12) configured using Sonnet’s Fully Human Albumin Binding (FHAB) technology (Press release, Sonnet BioTherapeutics, MAR 16, 2022, View Source [SID1234610175]). This will allow Sonnet to initiate its First-in-Human Phase 1 trial in adult oncology patients in the second quarter of 2022.

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"The FDA’s acceptance of the IND for SON-1010 is an important milestone in the development of our lead FHAB asset, signifying the evolution of Sonnet into a clinical biopharmaceutical company," said Pankaj Mohan, Ph.D., Founder and Chief Executive Officer. "We are excited about the progress we have made with our FHAB platform, which we believe will set the stage for improved efficacy of monospecific and bispecific cytokines, each differentiated by tumor targeting and retention in the tumor microenvironment."

The planned Phase 1 trial will be a multiple ascending dose study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of SON-1010 in adult patients with advanced solid tumors. "We have worked hard to establish a dose range for this extended PK form of IL-12 that can be tested safely and may provide an enhanced therapeutic index," said Richard Kenney, M.D., Sonnet’s Chief Medical Officer. "The goal of this strategy is to carefully adjust the body’s cells and cytokines to enhance the innate immune response to tumors." The study, utilizing a standard 3+3 oncology design in at least 5 cohorts, will establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) using monthly subcutaneous injections of SON-1010. The primary endpoint will assess the safety and tolerability of SON-1010, with key secondary endpoints planned to measure PK, PD, immunogenicity, and anti-tumor activity.

On March 16, 2022 Sana Biotechnology, Inc. (NASDAQ: SANA), a company focused on creating and delivering engineered cells as medicines, reported financial results and business highlights for the fourth quarter and year ended December 31, 2021 (Press release, Sana Biotechnology, MAR 16, 2022, View Source [SID1234610174]).

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"We are pleased with the progress we are making in our pipeline and in building capabilities to execute our vision of exploiting the potential of engineered cells to treat a number of diseases that don’t have effective treatments today," said Steve Harr, Sana’s President and Chief Executive Officer. "In 2021, we meaningfully strengthened our balance sheet, advanced our pipeline giving us the potential for two investigational new drug applications (INDs) in 2022 and multiple INDs per year going forward, built out our supply chain, including commercial access to gene-editing reagents and pluripotent stem cells, and commenced the build-out of our own manufacturing facility. Most importantly, we successfully attracted talent in key business areas, which, combined with the people already inside of the company, give us the capabilities, insights, focus, and dedication to reach our mission for patients."

Recent Corporate Highlights

Demonstrating forward progress in moving toward clinical trials for Sana’s multiple platforms including Sana’s ex vivo hypoimmune allogeneic CAR T, in vivo fusogen CAR T, and stem cell-derived programs:

Continued progress in building Sana’s hypoimmune ex vivo platform
Presented data in non-human primates showing survival and immune evasion, without immune suppression, of transplanted stem cells with Sana’s hypoimmune gene modifications.
Entered into a non-exclusive license and development agreement with FUJIFILM Cellular Dynamics, Inc. (FCDI) for access to FCDI induced pluripotent stem cells (iPSCs).
Gained access to gene editing capability to enable programs within Sana’s allogeneic CAR T and pluripotent stem cell portfolio through non-exclusive license for commercial rights to Beam Therapeutics Inc.’s (Beam) CRISPR Cas12b.
Progressed Sana’s hypoimmune allogeneic CD19-targeted CAR T program, SC291; IND expected as early as this year
Continue to progress on key steps required to advance to clinical trials, including contract manufacturing agreement for Phase I clinical supply, gene-editing reagent access through Beam license, Good Laboratory Practices (GLP) toxicology studies, and Good Manufacturing Practices (GMP) manufacturing processes and scale-up.
Presented data showing that hypoimmune CAR T cells evade both innate and adaptive immune systems in murine models, even in animals with pre-existing immunity to CAR T cells.
Presented data showing that CD19-targeted hypoimmune CAR T cells effectively kill tumor cells in mice and functionally evade the innate and adaptive immune system in allogeneic mouse recipients with either a murine or humanized immune system.
Progressed Sana’s in vivo CAR T program, SG295, utilizing a CD8-targeted fusosome to deliver a CD19-targeted CAR; IND expected as early as this year
Continue to progress on key steps to advance to clinical trials, including contract manufacturing agreement for Phase I clinical supply, GLP toxicology studies, and GMP manufacturing processes and scale-up.
Presented data highlighting ability of a single intravenous administration of a CD8-targeted fusosome containing a CD20-targeted CAR to deplete CD20+ B cells in NHPs.
Presented data highlighting ability of a single intravenous administration of SG295 to eliminate CD19+ tumor cells in mouse tumor models.
Expanded Sana’s CAR T capability to potentially develop best-in-class, broadly accessible CAR T cell therapies
Entered into an exclusive agreement with the National Institutes of Health (NIH) for worldwide commercial rights to the NIH’s CD22 chimeric antigen receptor with a fully-human binder. This CAR construct has shown efficacy in several clinical studies, including in CD19 CAR T cell therapy failures. Targeting both CD19 and CD22 with an "off-the-shelf" product, whether in combination with Sana’s hypoimmune platform or fusogen platform, offers the potential of higher and more durable complete response rates in earlier-stage patients as well as in patients that have previously failed an autologous CD19 CAR T cell therapy.
Entered into a non-exclusive agreement with IASO Biotherapeutics and Innovent Biologics for commercial rights to a clinically validated fully-human B cell maturation antigen (BCMA) CAR construct, which Sana intends to incorporate into both the company’s ex vivo hypoimmune allogeneic and in vivo fusogen platforms for the treatment of multiple myeloma.
Progressed Sana’s stem cell-derived pancreatic beta cell program, SC451, with potential to treat type 1 diabetes
Presented pre-clinical murine data demonstrating the ability to make stem cell-derived hypoimmune pancreatic islet cells with robust function and hypoimmune pancreatic islet cells that evade immune detection and have the ability to regulate glucose levels.
Established necessary agreements to establish GMP grade cell lines, including FCDI and Beam licenses, and secured contract manufacturing partner for cell bank production.
Remain on track for an IND as early as 2023.
Progressed Sana’s stem cell-derived cardiomyocyte program with the goal of treating heart failure
Presented data that demonstrated four edits in ion channels that alter the electrical properties of pluripotent stem cell-derived cardiomyocytes such that they eliminate engraftment arrythmias in a pig transplant model. These results demonstrate important progress in addressing a key risk associated with transplanting cardiomyocytes into the heart.
Strengthened balance sheet and Board leadership; signed lease to add internal manufacturing capability

Strengthened balance sheet with net proceeds of $626.6 million from the sale of 27 million shares of common stock in the company’s initial public offering.
Expanded Board of Directors with the addition of Joshua Bilenker, M.D., CEO of Treeline Biosciences, Alise Reicin, M.D., CEO of Tectonic Therapeutic, and Michelle Seitz, CFA, Chairman and CEO of Russell Investments.
Announced a lease agreement to develop a manufacturing facility in Fremont, California to support the manufacture of late-stage clinical development and early commercial product candidates across the multiple technologies in the pipeline.
Fourth Quarter 2021 Financial Results

GAAP Results

Cash Position: Cash, cash equivalents, and marketable securities as of December 31, 2021 were $746.9 million compared to $412.0 million as of December 31, 2020, an increase of $334.9 million. The increase was primarily driven by net proceeds of $626.4 million received in Sana’s initial public offering in February 2021, partially offset by cash used in operations of $201.1 million, a one-time upfront cash payment to Beam of $50.0 million to license its genome editing technology, and cash used for the purchase of property and equipment of $29.9 million.

Research and Development Expenses: For the three and twelve months ended December 31, 2021, research and development expenses, inclusive of non-cash expenses, was $108.5 million and $248.6 million, respectively, compared to $36.5 million and $132.9 million, respectively, for the same periods in 2020. The increases of $72.0 million and $115.7 million, respectively, for the three and twelve months ended December 31, 2021 were due to the one-time upfront payment to Beam to license its genome editing technology, an increase in personnel expenses related to increased headcount to expand Sana’s research and development capabilities, costs for laboratory supplies, costs for preclinical studies and external manufacturing, and facility costs. Research and development expenses include non-cash stock-based compensation of $5.3 million and $15.2 million, respectively, for the three and twelve months ended December 31, 2021 and $2.3 million and $4.9 million, respectively, for the same periods in 2020.

Research and Development Related Success Payments and Contingent Consideration: For the three months ended December 31, 2021, we recognized a non-cash gain of $9.9 million, and for the twelve months ended December 31, 2021, we recognized non-cash expense of $57.9 million, in connection with the change in the estimated fair value of the success payment liabilities and contingent consideration in aggregate, compared to expenses of $67.6 million and $124.9 million, respectively, for the same periods in 2020.

General and Administrative Expenses: General and administrative expenses for the three and twelve months ended December 31, 2021, inclusive of non-cash expenses, were $12.7 million and $50.4 million, respectively, compared to $9.2 million and $28.3 million, respectively, for the same periods in 2020. The increases of $3.5 million and $22.1 million, respectively, in the three and twelve months ended December 31, 2021 were primarily due to increased personnel-related expenses attributable to an increase in headcount to build our infrastructure and support our continued research and development activities, legal fees to support our patent portfolio and license arrangements, insurance associated with being a public company, consulting fees, and facility costs. General and administrative expenses include stock-based compensation of $2.0 million and $7.1 million, respectively, for the three and twelve months ended December 31, 2021 and $0.4 million and $0.9 million, respectively, for the same periods in 2020.

Net Loss: Net loss for the three and twelve months ended December 31, 2021 were $110.7 million, or $0.60 per share, and $355.9 million, or $2.14 per share, respectively, compared to $113.2 million, or $7.40 per share, and $285.3 million, or $21.92 per share, respectively, for the same periods in 2020.
Non-GAAP Measures

Non-GAAP Operating Cash Burn: Non-GAAP operating cash burn for the twelve months ended December 31, 2021 was $209.6 million compared to $125.0 million for the same period in 2020. Non-GAAP operating cash burn is the decrease in cash, cash equivalents, and marketable securities, excluding cash inflows from financing activities, cash outflows from business development activities, and the purchase of property and equipment.

Non-GAAP Research and Development Expenses: Non-GAAP research and development expenses for the three and twelve months ended December 31, 2021 were $108.5 million and $248.6 million, respectively, compared to $36.5 million and $123.0 million, respectively, for the same periods in 2020. Non-GAAP research and development expenses excludes certain one-time costs to acquire technology.

Non-GAAP Net Loss: Non-GAAP net loss for the three and twelve months ended December 31, 2021 was $120.6 million, or $0.65 per share, and $298.1 million, or $1.79 per share, respectively, compared to $45.5 million, or $2.98 per share, and $150.4 million, or $11.56 per share, respectively, for the same periods in 2020. Non-GAAP net loss excludes certain one-time costs to acquire technology and non-cash expenses related to the change in the estimated fair value of contingent consideration and success payment liabilities.
A discussion of non-GAAP measures, including a reconciliation of GAAP and non-GAAP measures, is presented below under "Non-GAAP Financial Measures."

On March 16, 2022 Prelude Therapeutics Incorporated (Nasdaq: PRLD), a clinical-stage precision oncology company, reported its financial results for the fiscal year ended December 31, 2021 (Press release, Prelude Therapeutics, MAR 16, 2022, View Source [SID1234610173]).

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"With Prelude’s core competencies in cancer biology and medicinal chemistry, in approximately five years we have successfully created a highly differentiated diverse pipeline that includes five distinct targets and six proprietary small molecule compounds, each with best-in-class potential aimed at addressing clinically validated pathways for cancers with selectable underserved patients," stated Kris Vaddi, Ph.D., Chief Executive Officer of Prelude. "Given the clinical progress we made in 2021, we have made important strategic portfolio prioritization and resource allocation decisions focusing on select molecules and indications where we see the greatest need and most efficient path to establishing proof-of-concept. This includes selecting PRT811 as the lead candidate in our PRMT5 program and prioritizing development of the intravenous formulation of our MCL1 candidate, PRT1419, and rapidly selecting a Phase 2 dose for PRT2527, our CKD9 inhibitor, in selected patients with cancers dependent on CKD9."

"Our discovery team continued to exceed expectations by bringing two new candidates into our pipeline, a differentiated SMARCA2/BRM protein degrader and most recently, PRT3645, a differentiated, selective and highly brain penetrant CDK4/6 inhibitor. We remain on track to file Investigational New Drug applications for each of these molecules in 2022."

Dr. Vaddi added, "Dr. Jane Huang’s appointment as President and Chief Medical Officer strengthens our leadership team. Dr. Huang’s extensive experience in oncology drug development, strong associations within the oncology community and success in building high-performing clinical development and operational teams supports our commitment to discover and deliver safe and effective precision oncology medicines to patients with underserved cancers."

Program Highlights and 2022 Objectives

PRMT5: Prelude is prioritizing PRT811 for continued clinical development focusing on splicing mutated myeloid malignancies and solid tumors, including uveal melanoma, and IDH1 mutated high grade gliomas. Prelude intends to complete the data analyses of the ongoing expansion cohorts for PRT543, including adenoid cystic carcinoma (ACC). Prelude expects to report data for the PRMT5 program in 2H/2022.

MCL1: Prelude is prioritizing development of the intravenous (IV) formulation of PRT1419 which demonstrated a desirable pharmacokinetic, pharmacodynamic and safety profile with potential for differentiation from competitor compounds. Prelude plans to initiate a combination trial with venetoclax by mid-year and report data by year-end 2022.

CKD9: Prelude intends to complete enrollment in the Phase 1 dose escalation study and identify a recommended Phase 2 dose by 2H/2022.

CDK4/6: Prelude intends to file an Investigational New Drug (IND) application mid-year and initiate a Phase 1 trial in 2H/2022.

SMARCA2/BRM: Prelude plans to complete IND-enabling studies and submit an IND application by year-end 2022.

Corporate Update

On March 9, 2022, Prelude announced the appointment of Jane Huang, M.D., to the newly created position of President and Chief Medical Officer. Dr. Huang joins Prelude from BeiGene Ltd., where she served as Chief Medical Officer, Hematology. Currently, Dr. Huang serves as an Adjunct Clinical Assistant Professor in Thoracic Oncology at Stanford University.

Full Year 2021 Financial Results

Cash and Cash Equivalents: Cash and cash equivalents as of December 31, 2021 were $291.2 million. Following Prelude’s recently announced program prioritization initiatives, the Company has extended its cash guidance and anticipates that its existing cash, cash equivalents and marketable securities will fund Prelude’s operations into the second half of 2024.

Research and Development (R&D) Expenses: R&D expenses for the year ended December 31, 2021 increased $38.6 million to $86.8 million compared to $48.2 million for the year ended December 31, 2020. The increase year-over-year was primarily due to increased clinical research costs to support the advancement of Prelude’s clinical programs and related chemistry, manufacturing and other costs for the clinical trials, in addition to an increase in discovery-stage program expenses.

General and Administrative (G&A) Expenses: G&A expenses for the year ended December 31, 2021 increased by $16.4 million to $27.0 million compared to $10.6 million for the year ended December 31, 2020. The increase was primarily due to increased employee headcount and an increase in professional fees as Prelude expanded its operations to support R&D efforts and incurred additional costs associated with operating as a public company.

Net Loss: Net loss for the year ended December 31, 2021 was $111.7 million or $2.43 per share, compared with a net loss of $56.9 million, or $4.56 per share for the year ended December 31, 2020.

On March 16, 2022 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that results from the Phase 3 SIENDO study will be presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper)’s (ESMO) (Free ESMO Whitepaper) Virtual Plenary taking place on Thursday, March 17, 2022 (Press release, Karyopharm, MAR 16, 2022, View Source [SID1234610172]). The data will also be presented in a late-breaking abstract at the Society for Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer taking place March 18-21, 2022, in Phoenix, Arizona.

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Details for the presentations are as follows:

ESMO Virtual Plenary:

Title: Prospective double-blind, randomized phase III ENGOT-EN5/GOG-3055/SIENDO study of oral selinexor/placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer
Presenter: Professor Ignace Vergote, MD, PhD, Leuven University Hospitals, Leuven, Belgium
Date and Time: Thursday, March 17, 2022, 6:00pm-7:00pm CET/1:00pm-2:00pm ET

SGO 2022 Annual Meeting on Women’s Cancer:

Title: Prospective double-blind, randomized phase III ENGOT-EN5/GOG-3055/SIENDO study of oral selinexor/placebo as maintenance therapy after first-line chemotherapy for advanced or recurrent endometrial cancer
Presenter: Professor Ignace Vergote, MD, PhD, Leuven University Hospitals, Leuven, Belgium
Session Type: Oral Presentation
Session: Scientific Plenary IV: Late-Breaking Abstracts
Date and Time: Saturday, March 19, 2022, 5:19pm-5:27pm MT/7:19pm-7:27pm ET

Conference Call Information
Karyopharm will host a conference call Thursday, March 17, 2022, at 4:30 p.m. Eastern Time, to discuss the SIENDO study results. To access the conference call, please dial (888) 349-0102 (local) or (412) 902-4299 (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 accompanying 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 SIENDO Study

The Phase 3 SIENDO study (ENGOT-EN5/GOG-3055) is a multicenter, blinded, placebo-controlled, randomized study evaluating the efficacy and safety of selinexor as a maintenance therapy following chemotherapy in patients with advanced or recurrent endometrial cancer. The study enrolled 263 patients with primary stage IV or recurrent disease who had a partial or complete response after at least 12 weeks of standard taxane-platinum combination chemotherapy. Patients were randomized 2:1 to receive either maintenance therapy of 80mg of selinexor taken once weekly, or placebo, until disease progression. The primary endpoint of the study is statistically significant improvement of progression-free survival compared to placebo. The goal of the study was to demonstrate a hazard ratio of 0.6 or better. In partnership with Karyopharm, the study was initiated by the ENGOT group. In the U.S., the collaboration includes the GOG-F.

About Endometrial Cancer

Endometrial cancer is the most common cancer of the female reproductive organs in the U.S., with approximately 66,000 new cases expected in 2022 leading to nearly 13,000 deaths.1 In 2020, there were approximately 130,000 new cases and 29,000 deaths in Europe from endometrial cancer, while on a global scale there were 417,000 new cases and approximately 97,000 deaths.2 More than 90 percent of uterine body cancers occur in the endometrium, so the actual numbers for endometrial carcinoma cases and deaths are slightly lower than these estimates, which include both endometrial carcinomas and uterine sarcomas. Unlike other cancers that have decreased with preventative measures, endometrial cancer is on the rise.3 Risk factors include obesity, Type 2 diabetes, high-fat diets, use of tamoxifen and oral estrogens, and delayed menopause.4 While the majority of endometrial cancers are diagnosed at early stages, approximately 14,000 patients in the U.S. are diagnosed with advanced disease that cannot be fully removed using surgery.5 These patients, and those with recurrent disease, are treated with chemotherapy. Chemotherapy does not cure patients with endometrial cancer. The use of later lines of chemotherapy are intended to control symptoms rather than cure the disease. There are no approved therapies in the maintenance setting for patients with advanced or recurrent endometrial cancer. The current standard of care is a "watch and wait" approach.6

About XPOVIO (selinexor)

XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm’s Selective Inhibitor of Nuclear Export (SINE) compounds to be approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade (bortezomib) and dexamethasone (XVd) in patients with multiple myeloma after at least one prior therapy; (ii) in combination with dexamethasone in patients with heavily pre-treated multiple myeloma; and (iii) in patients with diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO in certain countries) has received regulatory approvals in a growing number of ex-U.S. territories and countries, including Europe, the United Kingdom, China, South Korea and Israel, and is marketed in those areas by Karyopharm’s global partners. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including myelofibrosis. 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 were 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.