On May 9, 2024 ALX Oncology Holdings Inc., ("ALX Oncology" or the "Company") (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, reported financial results for the first quarter ended March 31, 2024, and provided a corporate update (Press release, ALX Oncology, MAY 9, 2024, View Source [SID1234643034]).

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"We entered the quarter with a great deal of momentum having achieved a key validating development milestone for our platform asset evorpacept in Q4 2023 by reporting positive results in a prespecified randomized interim analysis of ASPEN-06’s Phase 2 clinical trial in advanced HER2-positive gastric/GEJ cancer, becoming the first CD47 blocker to demonstrate anti-tumor activity in a global randomized study in solid tumors," said Jason Lettmann, Chief Executive Officer of ALX Oncology. "On the heels of this outstanding accomplishment, our first quarter efforts were focused on ensuring optimal clinical and operational execution as we advance our robust and maturing clinical-stage pipeline of best-in-class oncology programs that are reporting multiple value inflection datapoints in the coming months."

First Quarter 2024 Highlights and Recent Developments

Reported positive data from an ongoing investigator-sponsored trial ("IST") Phase 1/2 clinical trial of evorpacept in combination with standard-of-care in patients with relapsed or refractory B-cell non-Hodgkin lymphoma ("R/R B-NHL") in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting on April 9, 2024, in San Diego.
Twenty patients with indolent (n=18) and aggressive (n=2) R/R B-NHL received evorpacept plus standard rituximab and lenalidomide ("R2").
Evorpacept plus R2 was well tolerated with a safety profile similar to historical R2.
The combination achieved promising initial activity with a best overall response rate ("ORR") of 94% and a complete response rate ("CRR") of 83% in patients with indolent R/R B-NHL (R2 historical CRR benchmark is 34%).
The clinical trial is conducted and sponsored by the University of Texas MD Anderson Cancer Center.
Received acceptance of two evorpacept abstracts from the 2024 American Society of Cancer Oncology ("ASCO") Annual Meeting taking place in Chicago from May 31-June 4, 2024.
Evorpacept plus enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma: Phase 1a dose escalation results
Session Type and Title: Poster Presentation – Genitourinary Cancer – Kidney and Bladder
Session Date and Time: Sunday, June 2, 2024, 9:00 AM – 12:00 PM CDT
Location: Hall A
Abstract Number: 4575 (ALX Oncology Sponsored Clinical Trial)
Results of a Phase 2 study of evorpacept (ALX148), cetuximab and pembrolizumab in patients with refractory microsatellite stable metastatic colorectal cancer
Session Type and Title: Poster Presentation – Gastrointestinal Cancer – Colorectal and Anal
Session Date and Time: Saturday, June 1, 2024, 1:30 PM – 4:30 PM CDT
Location: Hall A
Abstract Number: 3530 (IST conducted by the University of Colorado Cancer Center and sponsored by the Academic GI Cancer Consortium)
Announced initiation of a Phase 2 IST of neoadjuvant radiation and evorpacept in combination with KEYTRUDA (pembrolizumab) in patients with previously untreated and early-stage locally advanced, resectable, human papillomavirus-mediated oropharyngeal cancer.
The clinical trial is conducted and sponsored by the Hanna and Mark Gleiberman Head and Neck Cancer Center at the University of California, San Diego.
Announced appointment of Allison Dillon, Ph.D., as Chief Business Officer.
Upcoming Clinical Milestones for Evorpacept’s Development Pipeline

Urothelial Carcinoma – Data from a Phase 1b ASPEN-07 clinical trial with PADCEV (enfortumab vedotin-ejfv) (ASCO: Embargo to lift on full abstract May 23, 2024; Poster to be presented on June 2, 2024)
Gastric/Gastroesophageal Junction ("GEJ") Cancer – Top line results from all 122 subjects in a Phase 2 randomized clinical trial of ASPEN-06 (July 2024)
Breast Cancer – Top line results from a Phase 1b I-SPY TRIAL with ENHERTU (fam-trastuzumab deruxtecan-nxki) (Q4 2024)
Head and Neck Squamous Cell Carcinoma – Top line results from a Phase 2 randomized clinical trial of ASPEN-03 with KEYTRUDA (Q4 2024/Q1 2025)
Head and Neck Squamous Cell Carcinoma – Top line results from a Phase 2 randomized clinical trial of ASPEN-04 with KEYTRUDA and chemotherapy (Q4 2024/Q1 2025)
Gastric/GEJ Cancer – Initiation of Phase 3 registrational randomized clinical trial for evorpacept (Q4 2024)
First Quarter 2024 Financial Results:

Cash, Cash Equivalents and Investments: Cash, cash equivalents and investments as of March 31, 2024, were $184.5 million. Subsequent to March 31, 2024, the Company issued additional shares of common stock under its at-the-market ("ATM") offering for approximately $26.2 million in net proceeds, after deducting commissions. The Company believes its cash, cash equivalents and investments, recent proceeds from sales under its ATM offering, along with the ability to draw down an additional $40 million of its term loan are sufficient to fund planned operations well into Q1 2026.

Research and Development ("R&D") Expenses: R&D expenses consist primarily of pre-clinical, clinical and manufacturing expenses related to the development of the Company’s current lead product candidate, evorpacept, and R&D employee-related expenses. These expenses for the three months ended March 31, 2024, were $31.7 million, compared to $24.8 million for the prior-year period. The $6.9 million increase was primarily attributable to increased clinical development costs from an increased number of active trials and patient enrollment as well as manufacturing of clinical trial materials to support a higher number of active clinical trials and future expected patient enrollment related to evorpacept, an increase of in personnel and related costs primarily driven by headcount growth, an increase in stock-based compensation expense related to a reclassification of stock-based compensation from G&A to R&D because of the change in roles for our former Chief Executive Officer who transitioned to the Chief Scientific Officer in September 2023, and an increase in other research costs primarily due to a development milestone payment related to ScalmiBio.

General and Administrative ("G&A") Expenses: G&A expenses consist primarily of administrative employee-related expenses, legal and other professional fees, patent filing and maintenance fees, and insurance. These expenses for the three months ended March 31, 2024, were $6.0 million, compared to $7.4 million for the prior year period. The $1.4 million decrease was primarily due to lower stock-compensation expense related to a reclassification of stock-based compensation which increased R&D stock-based compensation as detailed under R&D expenses.
Net loss: GAAP net loss was $35.6 million for the three months ended March 31, 2024, or ($0.71) per basic and diluted share, as compared to a GAAP net loss of $30.2 million for the three months ended March 31, 2023, or ($0.74) per basic and diluted share. Non-GAAP net loss was $28.5 million for the three months ended March 31, 2024, as compared to a non-GAAP net loss of $23.8 million for the three months ended March 31, 2023. A reconciliation of GAAP to non-GAAP financial results can be found at the end of this news release.

On May 9, 2024 XOMA Corporation (NASDAQ: XOMA), the biotech royalty aggregator, reported its first quarter 2024 financial results and highlighted recent activities (Press release, Xoma, MAY 9, 2024, View Source [SID1234643021]).

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"We continue to build the foundation for accelerating value creation with a disciplined approach to capital deployment," stated Owen Hughes, Chief Executive Officer of XOMA. "In recent months, we’ve completed the acquisition of Kinnate, acquired economic interests in two commercial assets, as well as in two first-in-class Phase 3 assets, and initiated our first share buyback program on the heels of securing the VABYSMO royalty-backed loan with Blue Owl. Lastly, and most importantly, the FDA approved OJEMBA (tovorafenib), Day One Biopharmaceuticals’ type II RAF inhibitor for patients with relapsed or refractory pLGG harboring a BRAF fusion or rearrangement or BRAF V600 mutation, ushering in an important new treatment for children living with relapsed or refractory pLGG."

Key First Quarter Events

Partner

Event

Talphera XOMA added another commercial asset to its royalty portfolio with an economic interest in DSUVIA, which is marketed by Alora Pharmaceuticals. XOMA receives 100 percent of the DSUVIA economics until a threshold is achieved; thereafter, XOMA retains the 15 percent royalty associated with DSUVIA commercial sales. The 75 percent royalties from Department of Defense purchases and remaining milestone payments will be shared equally between XOMA and Talphera.
Kinnate Pharmaceuticals XOMA initiated the acquisition of Kinnate Pharmaceuticals for $2.5879 in cash per share, plus a non-tradeable contingent value right (CVR) representing the right to receive 85 percent of the net proceeds from the out license or sale of Kinnate assets effected on or before April 2, 2025, and 100% of the net proceeds received from Pierre-Fabre.
Zevra Therapeutics U.S. Food and Drug Administration (FDA) accepted the arimoclomol NDA resubmission for review and set a Prescription Drug User Fee Act (PDUFA) action date of September 21, 2024. XOMA paid a $1 million milestone to LadRx based upon the achievement of this milestone.
Medexus FDA approved the pediatric label expansion application for IXINITY [coagulation factor IX (recombinant)].
Takeda Reported positive topline results from Phase 2 study evaluating mezagitamab (TAK-079), a potential best-in-class anti-CD38 monoclonal antibody for primary immune thrombocytopenia (ITP).i
LG Chem (AVEO Oncology) Dosed the first patient in the ficlatuzumab Phase 3 study, resulting in a $1 million milestone payment to XOMA.
Compugen Received a $1 million milestone payment from Compugen.
Subsequent Events

Partner

Event

Day One Biopharmaceuticals FDA approved Day One’s OJEMDA (tovorafenib) for use in pediatric patients with pediatric low-grade glioma (pLGG). XOMA earned a $9 million milestone upon the approval and is entitled to receive mid-single digit royalties from OJEMDA sales.
Daré Bioscience XOMA added economic interests to three best- or first-in-category assets to its portfolio. XACIATO vaginal gel 2% is commercially available and marketed by Organon. Bayer holds the U.S. rights to commercialize Ovaprene, a hormone-free monthly intravaginal contraceptive, currently in Phase 3 clinical trials. XOMA also acquired a synthetic royalty in Sildenafil Cream, 3.6%, a Phase 3-ready asset for female sexual arousal disorder.
Rezolute Dosed first patient in its Phase 3 trial of RZ358; XOMA earned a $5.0 million milestone associated with the event.
Anticipated 2024 Events of Note

Partner

Event

Zevra Therapeutics September 21, 2024 – FDA PDUFA action date for arimoclomol NDA
Takeda In its press release dated March 13, 2024, Takeda announced plans to initiate a global Phase 3 trial of mezagitamab in ITP in fiscal year 2024.ii
First Quarter 2024 Financial Results

XOMA recorded total revenues of $1.5 million for the first quarter of 2024, which included a $1.0 million milestone payment received from AVEO Oncology, as compared with $0.4 million in the first quarter of 2023.

Research and development (R&D) expenses were $33,000 and $54,000, respectively, for the first quarters of 2024 and 2023. Upon closing the Kinnate merger in the second quarter of 2024, XOMA assumed operations of Kinnate’s pipeline, as well as ongoing Phase 1 study, and will incur increased R&D costs until winddown activities are complete.

General and administrative ("G&A") expenses were $8.5 million for the first quarter of 2024, compared to $6.2 million for the first quarter of 2023. The increase of $2.3 million was primarily due to a $1.3 million increase in stock-based compensation and a $0.7 million increase in consulting and legal expenses. The increase in stock-based compensation expenses was largely due to the appointment of Mr. Hughes as our full-time Chief Executive Officer in January 2024.

In the first quarter of 2024, G&A expenses included $2.9 million in non-cash stock-based compensation expense, compared with $1.6 million in the first quarter of 2023. The increase in stock-based compensation expenses was largely due to the PSU grant associated with the appointment of Mr. Hughes as our full-time Chief Executive Officer in January 2024 combined with PSUs granted in May 2023.

Interest expense in the first quarter of 2024 was $3.6 million, representing interest related to the Blue Owl Loan established in December 2023.

The Company reported total other income, net, of $2.0 million in the first quarter of 2024, as compared to total other income, net, of $0.4 million in the corresponding period of 2023. The $1.6 million increase reflects a $1.3 million increase in investment income due to higher cash balances and higher market interest rates on our investments, as well as the change in the market price of Rezolute’s common stock.

Net loss for the first quarter of 2024 was $8.6 million, compared to a net loss of $9.8 million for the first quarter of 2023.

On March 31, 2024, XOMA had cash and cash equivalents of $142.4 million (including $6.2 million in restricted cash). On December 31, 2023, XOMA had cash and cash equivalents of $159.6 million (including $6.3 million in restricted cash). During the first quarter of 2024, XOMA received $9.8 million in cash from royalty and milestone payments and deployed $8 million to acquire new royalty and milestone economic interests. Net cash used in operating activities during the quarter was $4.9 million. On April 15, 2024, the Company paid a total of $1.4 million in cash dividends on the 8.625% Series A Cumulative Perpetual Preferred Stock (Nasdaq: XOMAP) and the 8.375% Series B Cumulative Perpetual Preferred Stock (Nasdaq: XOMAO).

On May 9, 2024 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, reported financial results for the first quarter ended March 31, 2024 and provided a review of recent clinical and business highlights (Press release, Xencor, MAY 9, 2024, View Source [SID1234643020]).

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"We have focused our XmAb clinical pipeline and discovery activities on bispecific CD3 and CD28 T cell engagers, which continue to show clinical validation for their potential in treating patients with serious diseases. Our key clinical-stage oncology programs in solid tumors include XmAb819 (ENPP3 x CD3) in clear cell renal cell carcinoma, XmAb808 (B7-H3 x CD28) in prostate cancer and other cancers, and XmAb541 (CLDN6 x CD3) in ovarian cancer and other cancers, which are all now advancing in Phase 1 clinical studies. We plan to select our next T cell engager IND candidate later this year," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Additionally, Xencor’s best-in-class Xtend antibody half-life extension technology continues to support improved outcomes for patients, with Ultomiris now approved in the U.S. for certain patients with NMOSD, and we are especially delighted by recently published results demonstrating an investigational antibody with Xtend was effective in preventing malaria."

Recent Clinical and Business Highlights
•First Patient Dosed in Phase 1 Study of XmAb541 (CLDN6 x CD3): XmAb541 is a bispecific antibody being developed for patients with CLDN6-positive tumors including advanced ovarian cancer. XmAb541 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing Claudin-6 (CLDN6), a tumor-associated antigen. Xencor’s XmAb 2+1 multivalent format used in XmAb541 enables greater selectivity for cells expressing CLDN6 over similarly structured Claudin family members, which may be expressed on normal tissue. The first patient was recently dosed in a Phase 1 dose-escalation study.

•FDA Approves Ultomiris (Alexion Pharmaceuticals, Inc.) for Adults with NMOSD: In March 2024, Ultomiris (ravulizumab-cwvz), which incorporates Xencor’s Xtend Fc Domain, was approved in the United States as the first and only long-acting C5 complement inhibitor for the treatment of adult patients with anti-aquaporin-4 (AQP4) antibody-positive (Ab+) neuromyelitis optica spectrum disorder (NMOSD). Ultomiris is also approved for certain adults with NMOSD in Japan and the European Union (EU). As part of Xencor’s recent Ultomiris royalty monetization, the Company remains eligible for certain future royalties and milestone payments. Ultomiris is a registered trademark of Alexion Pharmaceuticals, Inc.

•Single Dose of Investigational Antibody with Xtend Confers Protection Against Malaria Infection: Results from a Phase 2 National Institutes of Health (NIH)-sponsored clinical trial published in the New England Journal of Medicine showed that a single dose of L9LS, an experimental monoclonal antibody that incorporates Xencor’s Xtend Fc Domain, was up to 77% effective in preventing malaria in children in Mali for six months, demonstrating the long duration of action that Xtend technology can provide.

•New Chief Financial Officer Appointed: Bart Cornelissen was appointed as Xencor’s senior vice president and chief financial officer. He was most recently vice president, corporate finance at Seagen Inc.
Financial Guidance: Based on current operating plans, Xencor expects to end 2024 with between $475 million and $525 million in cash, cash equivalents and marketable debt securities, and to have cash to fund research and development programs and operations into 2027.
Financial Results for the First Quarter Ended March 31, 2024
Cash, cash equivalents and marketable debt securities totaled $646.7 million as of March 31, 2024, compared to $697.4 million on December 31, 2023.
Revenues for the first quarter ended March 31, 2024 were $12.8 million, compared to $19.0 million for the same period in 2023. Total revenues earned in the first quarter of 2024 included non-cash royalty revenue from Xencor’s Alexion and Morphosys/Incyte agreements, compared to milestone revenue earned from the J&J collaboration and royalties from the Alexion agreement in the first quarter of 2023.
Research and development expenses for the first quarter ended March 31, 2024 were $56.9 million, compared to $65.6 million for the same period in 2023. Decreased research and development spending for the first quarter of 2024 compared to 2023 reflects changes in spending across multiple clinical-stage programs and wind-down costs on terminated programs.
General and administrative expenses for the first quarter ended March 31, 2024 were $13.8 million and were in line with $14.2 million for the same period in 2023.
Other expense, net, for the first quarter ended March 31, 2024 was $10.8 million, compared to $0.02 million for the same period in 2023. Increased other expense for the first quarter of 2024 compared to 2023 reflects impairment charge on equity investments, partially offset by interest income earned on investments and unrealized gain on equity investments.

Non-cash, stock-based compensation expense for the first quarter ended March 31, 2024 was $11.4 million, compared to $12.6 million for the same period in 2023.

Net loss for the first quarter ended March 31, 2024 was $68.0 million, or $(1.11) on a fully diluted per share basis, compared to $60.8 million, or $(1.02) on a fully diluted per share basis, for the same period in 2023.

The total shares outstanding were 61,634,685 as of March 31, 2024, compared to 60,381,600 as of March 31, 2023.
Upcoming Investor Conferences
Company management will participate at multiple upcoming investor conferences:
•RBC Capital Markets Global Healthcare Conference
Date: Tuesday, May 14, 2024
Presentation Time: 2:05 p.m. ET / 11:05 a.m. PT
Location: New York City
•BofA Securities Health Care Conference
Date: Wednesday, May 15, 2024
Presentation Time: 4:40 p.m. ET / 1:40 p.m. PT
Location: Las Vegas

Live webcasts of the presentations will be available under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com. Replays of the events will be available on the Xencor website for at least 30 days following the presentations.

On May 9, 2024 Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-classi targeted and immune-mediated therapeutics to fight cancer, reported financial results for the quarter ended March 31, 2024, and provided a corporate update (Press release, Tempest Therapeutics, MAY 9, 2024, View Source [SID1234643019]).

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"The positive data and mechanistic analysis presented in the first quarter build on the positive preclinical and clinical data package for TPST-1120, further confirming and reinforcing our excitement about the potential of TPST-1120 in liver and kidney cancers, as well as other indications, and our confidence in the program as it moves closer to a pivotal Phase 3 study in first-line HCC," said Stephen Brady, president and chief executive officer of Tempest.

Recent Highlights

TPST-1120 (clinical PPARα antagonist):
Reported new preclinical data at the 2024 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that TPST-1120 reduces kidney cancer (RCC) growth as a monotherapy, while also showing increased inhibition when combined with frontline chemotherapy and immunotherapy. These data further support the clinical benefit observed in the TPST-1120 Phase 1 data presented in an oral presentation at ASCO (Free ASCO Whitepaper) 2022.
Published positive data from Phase 1 Trial of TPST-1120 in patients with advanced solid tumors in the Journal of Cancer Research Communications. Data showed that TPST-1120 demonstrated clinical activity, including tumor shrinkage, even in PD-1 inhibitor-refractory and immune-compromised cancers, and was well tolerated both as monotherapy and in combination with nivolumab. These data complement the positive Phase 1b/2 data reported in October 2023 from a global randomized study of TPST-1120 in combination with atezolizumab and bevacizumab in first-line patients with advanced HCC.
Presented new preclinical data showing potent anti-tumor activity in several cancer models treated with TPST-1120 alone or with immune checkpoint inhibitors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Spring Scientific Meeting. The presentation also covered experimental results that corroborated clinical biomarker data from patients with advanced solid tumor cancers treated in the Phase 1 clinical trial of TPST-1120 in multiple solid tumor indications, which showed statistically significant, exposure-dependent elevations in expression levels of multiple immune-related genes, and patients exhibiting objective responses displayed increased circulating free fatty acids (FFA), both of which are in-line with the proposed TPST-1120 mechanism of action.
Potential Future Milestones

TPST-1120 (clinical PPARα antagonist)
Expect to announce updated data from the ongoing randomized study in first-line HCC patients in 2024.
Plan to advance TPST-1120 into a registrational Phase 3 study in first-line HCC patients, subject to obtaining feedback from the FDA.
TPST-1495 (clinical dual EP2/4 prostaglandin receptor antagonist)
Plan to advance TPST-1495 into a Phase 2 study in patients with Familial Adenomatous Polyposis ("FAP") in 2024 under the auspices of the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute ("NCI") Division of Cancer Prevention, subject to final approval of NCI.
Expect to report data from the combination arm at the two highest TPST-1495 doses in patients with advanced endometrial cancer, where prostaglandin signaling is implicated, in 2024.
Financial Results

First Quarter 2024

Tempest ended the quarter with $32.3 million in cash and cash equivalents, compared to $39.2 million on December 31, 2023.
Net loss and net loss per share for the quarter ended March 31, 2024, were $7.9 million and $0.36, respectively, compared to $7.6 million and $0.55, respectively, for the same period in 2023.
Research and development expenses for the quarter were $4.3 million compared to $4.7 million for the same period in 2023. The $0.4 million decrease was primarily due to a decrease in costs incurred from contract research organizations and third-party vendors.
General and administrative expenses for the quarter were $3.6 million compared to $2.9 million for the same period in 2023. The $0.7 million increase was primarily due to share-based compensation expenses and consulting services.
Based on its current cash and operating plan, Tempest expects to have sufficient resources to fund operations into the second quarter of 2025.

On May 9, 2024 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported financial results for the first quarter of 2024 and provided a business update (Press release, Viracta Therapeutics, MAY 9, 2024, View Source [SID1234643018]).

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"Our near-term goal is to address the high unmet medical needs of patients living with relapsed or refractory EBV-positive PTCL by advancing Nana-val through regulatory approval as quickly as possible," said Mark Rothera, President and Chief Executive Officer of Viracta. "Topline results from Stage 1 of the ongoing pivotal Phase 2 NAVAL-1 trial provided a strong signal of efficacy with a generally well-tolerated safety profile that were consistent with outcomes from the prior Phase 1b/2 study of Nana-val. The observed objective and complete response rates of Nana-val far exceeded the nanatinostat monotherapy arm, further validating the combined mechanism of action of Nana-val treatment. We look forward to sharing additional data from Stage 1, which continue to mature, as well as initial results from Stage 2 in the third quarter of 2024. We are encouraged by the growing data from the NAVAL-1 trial that underscore the benefit of Nana-val, our first-in-class, all-oral combination treatment regimen, and plan to engage with the FDA on a potential accelerated approval pathway in mid-2024."

Clinical Trial Updates and Anticipated Milestones

Pivotal Phase 2 NAVAL-1 trial of Nana-val (nanatinostat in combination with valganciclovir) in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma

Clinical Trial Updates:

•
Presented positive topline Stage 1 data from both arms of the R/R EBV+ peripheral T-cell lymphoma (PTCL) cohort, patients randomized to either nanatinostat monotherapy (n=10) or to nanatinostat in combination with valganciclovir (Nana-val, n=10), at the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan.

o
As of the February 7, 2024 data cutoff date, Nana-val (nanatinostat in combination with valganciclovir) demonstrated greater efficacy than nanatinostat alone and was generally well-tolerated. The median duration of response (DoR) continues to mature.
▪
In the Nana-val arm, the objective response rate (ORR) was 50% and the complete response rate (CRR) was 20% in the intent-to-treat population, while the ORR was 71% and the CRR was 29% in the efficacy-evaluable population.
▪
In the nanatinostat monotherapy arm, the ORR and CRR were 10% and 0% in the intent-to-treat population, while the ORR was 13% in the efficacy-evaluable population.
o
Data also showed that Nana-val was generally well tolerated, with the most common treatment-related adverse events in both treatment arms of thrombocytopenia, anemia, fatigue, decreased appetite, nausea, diarrhea, and weight loss.
▪
These adverse events were primarily mild to moderate in severity and generally manageable or reversible.
▪
The type, frequency, and severity of these adverse events were generally consistent with those from over 135 patients with R/R EBV+ lymphomas who have been treated with Nana-val to date.
Anticipated 2024 Milestones:

•
Engage with U.S. Food and Drug Administration (FDA) in mid-2024 to align on requirements for accelerated approval.
•
Enroll patients into the post-Phase 2 expansion cohort to support potential accelerated approval.
•
Present Stage 1 + Stage 2 data (n=21) in the R/R EBV+ PTCL cohort in patients treated with Nana-val in the third quarter of 2024.
•
Report Stage 1 data from patients with R/R EBV+ diffuse large B-cell lymphoma (DLBCL) and R/R EBV+ post-transplant lymphoproliferative disorder (PTLD) by year-end 2024.

Phase 1b/2 trial of Nana-val in patients with recurrent/metastatic (R/M) EBV+ nasopharyngeal carcinoma (NPC) and other advanced EBV+ solid tumors (Study 301)

Clinical Trial Updates:

•
Completed enrollment of the sixth dose cohort from the Phase 1b dose escalation portion of the trial evaluating the novel split daily dosing (SDD) regimen in patients with R/M EBV+NPC.
•
Started enrolling patients into the seventh dose cohort also evaluating the SDD regimen in the Phase 1b dose escalation portion of the trial.
Anticipated 2024 Milestones:

•
Determine the recommended Phase 2 dose (RP2D) in the second half of 2024.
•
Initiate a dose-optimization cohort to confirm the RP2D as part of the study’s Phase 2 expansion by year-end 2024.

Business Updates

•
Engaged with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) on the extension of the NAVAL-1 trial into Japan.
o
At a recent meeting, the PMDA endorsed the enrollment of patients in Japan into the NAVAL-1 trial without a preceding Japanese Phase 1 safety/pharmacokinetics study.
o
Viracta plans to engage with the PMDA in the second half of 2024 to align on a potential approval pathway for Nana-val in R/R EBV+PTCL.

▪
The PMDA has granted full approval for R/R PTCL drugs based on a primary ORR endpoint supported by DoR and safety in single-arm studies.

First Quarter 2024 Financial Results

•
Cash position – Cash, cash equivalents, and short-term investments totaled approximately $39.6 million as of March 31, 2024, which Viracta expects will be sufficient to fund operations late into the first quarter of 2025.
•
Research and development expenses –Research and development expenses were approximately $10.0 million for the three months ended March 31, 2024, compared to approximately $7.6 million for the three months ended March 31, 2023. The increase in research and development expenses was largely due to a non-cash adjustment for insurance costs related to the February 2021 reverse merger with Sunesis Pharmaceuticals of $1.8 million, as well as increases in costs incurred to support the advancement and expansion of our clinical development programs, including incremental costs to support NAVAL-1, our pivotal Phase 2 trial of Nana-val in patients with R/R EBV+ lymphomas.
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General and administrative expenses – General and administrative expenses were approximately $3.9 million for the three months ended March 31, 2024, compared to $4.6 million for the same period in 2023. The decrease in general and administrative expenses was largely due to lower corporate liability insurance premiums and legal costs.
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Net loss – Net loss was approximately $9.1 million, or $0.23 per share (basic and diluted), for the quarter ended March 31, 2024, compared to a net loss of $12.2 million, or $0.32 per share (basic and diluted), for the same period in 2023. This change was primarily the result of $5.0 million of other income received related to the monetization of a pre-commercialization, event-based milestone from Day One Biopharmaceuticals, Inc. in March 2024, partially offset by the non-cash adjustment for insurance costs related to the February 2021 merger of $1.8 million.

About the NAVAL-1 Trial

NAVAL-1 (NCT05011058) is a global, multicenter, clinical trial of Nana-val in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphoma. This Phase 2 trial employs a Simon two-stage design where, in Stage 1, participants are enrolled into one of three indication cohorts based on EBV+ lymphoma subtype. If two objective responses are achieved within a lymphoma subtype in Stage 1 (n=10), then additional patients will be enrolled in Stage 2 for a total of 21 patients. EBV+ lymphoma subtypes demonstrating promising antitumor activity in Stage 2 may be further expanded following discussion with regulators to potentially support registration.

About the Phase 1b/2 Study of Nana-val in Patients with Advanced EBV+ Solid Tumors (Study 301)
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational clinical trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation part is designed to evaluate safety and to select the recommended Phase 2 dose (RP2D) of Nana-val in patients with recurrent or metastatic (R/M) Epstein-Barr virus-positive (EBV+) nasopharyngeal carcinoma (NPC). Along with the U.S. Food and Drug Administration’s Project Optimus initiative, at the start of Phase 2, up to 40 patients with R/M EBV+ NPC will be randomized to receive either the RP2D or a dose level below the RP2D in a dose-optimization cohort. Once the RP2D has been confirmed, up to 60 patients with R/M EBV+ NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to further evaluate antitumor activity, safety and tolerability, pharmacokinetics, and potential pharmacodynamic biomarkers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort.

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 are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (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 or refractory (R/R) EBV+ lymphoma (NAVAL-1) as well as a multinational Phase 1b/2 clinical trial in patients with recurrent or metastatic (R/M) EBV+ NPC and other advanced EBV+ solid tumors.

About Peripheral T-Cell Lymphoma

T-cell lymphomas comprise a heterogeneous group of rare and aggressive malignancies, including peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). There are approximately 5,600 newly diagnosed T-cell lymphoma patients and approximately 2,600 newly diagnosed PTCL-NOS and AITL patients in the U.S. annually. Approximately 70% of these patients are either refractory to first-line therapy, or eventually experience relapse of their disease. Clinical trials are currently recommended for all lines of PTCL therapy, and most patients with R/R PTCL have poor outcomes, with median progression-free survival and median overall survival times reported to be 3.7 and 6.5 months, respectively. Approximately 40% to 65% of PTCL is associated with EBV, the incidence of EBV+ PTCL varies by geography, and reported outcomes for patients with EBV+ PTCL are inferior to those whose disease is EBV-negative. There is no approved targeted treatment specific for EBV+ PTCL, and therefore this represents a high unmet medical need.

About EBV-Associated Cancers

Approximately 90% of the world’s adult population is infected with EBV. Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of 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-positive (EBV+) lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma (NPC), and gastric cancer.