On April 1, 2024 Lunit (KRX:328130.KQ), a leading provider of AI-powered solutions for cancer diagnostics and therapeutics, reported the presentation of seven studies at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting in San Diego, California, from April 5 to 10 (Press release, Lunit, APR 1, 2024, View Source [SID1234641674]).

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In a poster presentation, Lunit’s AI-powered HER2 analyzer, Lunit SCOPE HER2’s precision shines through its analysis of 194,259 pan-cancer samples, correlating different ERBB2 mutations with changes in HER2 protein expression. This AI-powered assessment successfully identified key mutation-expression correlations, particularly focusing on exon 20 insertions (ex20ins) and S310x mutations across a variety of cancers, including NSCLC, urothelial, and breast cancers.

Through detailed HER2 intensity examination, the AI analysis highlighted that, among ERBB2-mutated cases with HER2 IHC images, a higher proportion of HER2 3+ tumor cells was observed in S310x and ex20ins cases compared to others. Similarly, high HER2 expression was observed in both S301x and ex20ins cases compared to other mutation cases. The findings suggest that understanding these mutation-expression relationships could improve the prediction of treatment responses, enabling a step forward in the development of more personalized and precise therapeutic strategies for cancer patients with ERBB2 mutations. The study also indicates the potential of AI in enhancing the precision of cancer treatment through the identification of genetic alterations that influence protein levels.

In a collaborative study with Genome & Company, a clinical-stage biotechnology specializes in anti-cancer therapeutic development, Lunit leveraged its AI-powered immunohistochemistry (IHC) analyzer to investigate the expression of Contactin-4 (CNTN4) and its relationship with PD-L1 across 18 types of cancers. CNTN4, which is mainly expressed in tumor cells, is known to reduce T-cell activation and responsiveness to tumors.

The analysis of 795 pan-cancer tissue samples revealed an important inverse correlation between CNTN4 expression and PD-L1 levels. When PD-L1 intensity was ≥ 30%, 50%, 75%, and 90%, CNTN4 was observed in 42.4% (337/795), 25.5% (203/795), 11.4% (91/795), and 5.2% (41/795) of cases, respectively. This insight positions CNTN4 as a promising target for immunotherapy, particularly in cancers that exhibit low PD-L1 expression.

Another study conducted with Genome & Company focused on the correlation between the efficacy of pembrolizumab treatment and CNTN4 expression in gastric cancer patients. This study categorized patients based on CNTN4 and PD-L1 expression levels. The results indicated that patients with low CNTN4 expression and high PD-L1 levels were more likely to respond favorably to pembrolizumab, showing a 64.3% objective response rate (ORR). Conversely, patients exhibiting both high CNTN4 and PD-L1 expression demonstrated a 0% ORR, with non-responders presenting lower PD-L1 expression and higher CNTN4 levels compared to responders. These findings not only highlight CNTN4’s potential as a predictive biomarker for immunotherapy response but also underscore the pivotal role of AI-powered analytics in identifying novel biomarkers.

"We are excited to present our groundbreaking studies at AACR (Free AACR Whitepaper) 2024, illustrating the profound impact of the Lunit SCOPE suite on cancer research and treatment," said Brandon Suh, CEO of Lunit. "Our findings, particularly the discovery of key mutation-expression correlations by Lunit SCOPE HER2 and the potential of CNTN4 as a novel biomarker for immunotherapy responsiveness, underscore our commitment to transforming cancer care. These studies not only highlight our pioneering role in leveraging AI to enhance precision medicine but also pave the way into the future of oncology – where treatment is not just personalized but predictive, ensuring the best possible outcomes for patients worldwide. We’re proud to contribute to this transformative journey, marking a significant milestone in our mission to fight cancer with AI."

In addition to the studies above, Lunit will present four more studies at this year’s AACR (Free AACR Whitepaper), showcasing the diverse capabilities of Lunit SCOPE IO, Lunit SCOPE HER2, and an AI-based CT image analyzer combining analysis of CT scans with digital pathology analysis to predict response to checkpoint therapy.

Visit Lunit at booth 808 to explore how the Lunit SCOPE suite is revolutionizing oncology research and clinical practice.

Presentations at AACR (Free AACR Whitepaper) 2024 featuring Lunit SCOPE include:

"Pan-Cancer analysis of the influence of ERBB2 alteration on HER2 expression" (4640/16, Section 26, April 9, 9:00 AM – 12:30 PM)
"Association of artificial intelligence (AI)-based HER2 scoring with clinical outcomes to first-line trastuzumab plus chemotherapy in HER2-positive metastatic gastric cancer (mGC)" (2484/1, Section 43, April 8, 9:00 AM – 12:30 PM)
"Assessment of CNTN4 expression and its association with PD-L1 across 18 various cancers using an artificial intelligence-powered immunohistochemistry analyzer" (553/6, Section 23, April 7, 1:30 PM – 5:00 PM)
"Association between the CNTN4 expression and responsiveness to pembrolizumab in gastric cancer" (7522/10, Section 42, April 10, 9:00 AM – 12:30 PM)
"Artificial intelligence (AI)-based multi-modal approach using H&E and CT image for predicting treatment response of immune checkpoint inhibitor (ICI) in non-small cell lung cancer (NSCLC)" (4170/25, Section 8, April 9, 9:00 AM – 12:30 PM)
"Artificial intelligence-powered analysis of tumor-stroma ratio and fibroblast density as prognostic indicators in colorectal cancer" (276/7, Section 11, April 7, 1:30 PM – 5:00 PM)
"Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a prognostic biomarker for pembrolizumab plus chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma" (7658/19, Section 46, April 10, 9:00 AM – 12:30 PM)

On April 1, 2024 aTyr Pharma, Inc. (Nasdaq: LIFE), a clinical stage biotechnology company engaged in the discovery and development of first-in-class medicines from its proprietary tRNA synthetase platform, reported that the company will participate in two upcoming investor conferences scheduled to take place in April 2024 (Press release, aTyr Pharma, APR 1, 2024, View Source [SID1234641673]).

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Details of the conferences appear below:

Conference: Evercore ISI Diamonds in the Rough Webinar Day
Date: Thursday, April 4, 2024
Time: 10:30am EDT
Location: Virtual
Format: Corporate Presentation with Q&A Session

Conference: Piper Sandler Spring Biopharma Symposium
Date: Wednesday, April 17, 2024
Location: Everett, MA
Format: 1×1 Investor Meetings

For more information on how to register, please contact your Evercore ISI or Piper Sandler representative.

On April 1, 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 that topline results from Stage 1 of the NAVAL-1 trial of Nana-val (nanatinostat in combination with valganciclovir) in patients with relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma (PTCL) will be featured in an oral presentation during the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan (Press release, Viracta Therapeutics, APR 1, 2024, View Source [SID1234641669]). Details of the presentation are as follows:

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Title: A Global Phase 2 Trial of Nanatinostat in Combination with Valganciclovir in Patients with EBV-Positive (EBV+) Relapsed/Refractory Peripheral T-Cell Lymphomas (NAVAL-1)
Format: Oral presentation
Presenting Author: Professor Hung Chang, M.D., principal investigator in the NAVAL-1 trial, Chief of the Hematology Division, Linkou Chang Gung Memorial Hospital and Visiting Scholar at UMass Memorial Health Care
Presentation Date and Time: Saturday, April 13, at 10:12 a.m. China Standard Time (Friday, April 12, at 7:12 p.m. Pacific Daylight Time)
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 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 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 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.

On April 1, 2024 HCW Biologics Inc. (the "Company" or "HCW Biologics") (NASDAQ: HCWB), a clinical-stage biopharmaceutical company focused on discovering and developing novel immunotherapies to lengthen healthspan by disrupting the link between inflammation and age-related diseases, reported financial results and recent business highlights for its fourth quarter and fiscal year ended December 31, 2023 (Press release, HCW Biologics, APR 1, 2024, View Source [SID1234641667]).

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Dr. Hing C. Wong, Founder and CEO of HCW Biologics, stated, "These are exciting times at HCW Biologics. We achieved two major clinical milestones, with the completion of the Phase 1 clinical study to evaluate HCW9218 in solid tumors and the Phase 1b study to evaluate HCW9218 in pancreatic cancer. While it is still quite early in the clinical development process and we have only seen data when HCW9218 is administered as a monotherapy, we believe there are signs that HCW9218 provides clinical benefits to patients who have previously failed multiple lines of standard-of-care therapies. We believe that HCW9218 shows the potential to be a first in class immunotherapeutic cancer treatment."

Dr. Wong continued, "Now we are on the verge of initiating multiple Phase 2 clinical studies, including randomized trials, to evaluate HCW9218 as a treatment in combination with standard-of-care therapy in patients with cancer. We intend to focus on ovarian and pancreatic cancer, and we hope to opportunistically join studies with investigators who want to add an arm to their study using HCW9218 in combination with their therapy. This approach could give us an opportunity to assess HCW9218 in more cancer indications that we believe will provide valuable data to inform us of the most appropriate indications and regimens for future registration trials."

"Another piece of exciting news for 2024 is that we are planning on the initiation of investigative studies for age-related diseases using HCW9218. We are planning on using the Recommended Phase 2 Dose level of HCW9218 identified in our two now completed Phase 1/1b cancer trials. Dr. Wong added. "We believe age-associated dermatological conditions and diseases, such as senile lentigo and deep wrinkles, will be the first age-related indications we investigate beyond cancer.

Business Highlights

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The Phase 1 clinical trial to evaluate HCW9218 in solid tumors and the Phase 1b clinical trial to evaluate HCW9218 in pancreatic cancer were completed in February 2024. In the Phase 1 study, over 70% of patients with ovarian cancer (5/7) showed evidence of stable disease. In the Phase 1b study, 13% (2/15) of patients who participated in the study showed evidence of stable disease.
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The first Phase 2 clinical study to evaluate HCW9218 in patients with ovarian cancer will be sponsored by the University of Pittsburgh Medical Center. This fully randomized trial will have one arm of the study treating patients with HCW9218 with a neoadjuvant chemotherapy.
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The Company’s investment in its patent portfolio is beginning to result in new patent awards from the USPTO. Most importantly, among the patents the Company was awarded are the fundamental patents which protect the technology on which the Company’s lead molecules are based.
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On January 10, 2024, the Company terminated the credit agreement with Prime Capital Ventures, whereupon the Company was entitled to receive a refund of $5.3 million that was funded to establish an interest reserve account under the terms of the credit agreement. Due to the probability of default, the Company recognized a reserve for credit losses of $5.3 million as of December 31, 2023. However, the Company intends to pursue available remedies to recover these funds.
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On February 20, 2024, the Company completed a $2.5 million private placement of its common stock, at a price of $1.40 per share, which was a 25% premium over the market price on the closing date. Investors included certain officers and directors of the Company.
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As of March 31, 2024, the Company entered into legally binding agreements to issue $10.0 million of secured notes from investors, including certain of our officers and directors as well as other investors, $2.0 million of which was funded by the issuance date of the audited financial statements.

Fourth Quarter 2023 and Year End Financial Results

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Revenues: Revenues for the fourth quarters ended December 31, 2022 and 2023 were $1.3 million and $1.3 million, respectively. Revenues for the years ended December 31, 2022 and 2023 were $6.7 million and $2.8 million, respectively. Revenues were derived exclusively from the sale of licensed molecules to the Company’s licensee, Wugen. The licensed molecules are one of the inputs for manufacturing Wugen’s products. In 2023, revenues were negatively impacted by changes in Wugen’s clinical development program. In addition, Wugen suffered delays in ramping up its manufacturing process which also limited purchases of molecules licensed by the Company.
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Research and development (R&D) expenses: R&D expenses for the fourth quarters ended December 31, 2022 and 2023 were $2.9 million and $2.1 million, respectively. The $793,616 decrease, or 27%, resulted from a decline in manufacturing and materials expense. R&D expenses for the years ended December 31, 2022 and 2023 were $9.4 million and $7.7 million, respectively. The $1.7 million decrease, or 18%, resulted from a decline in expenses related to manufacturing and materials expense, preclinical expenses and performance-based bonuses. Manufacturing costs declined in 2023 because the Company had already made the necessary supplies of its lead molecules, HCW9218 and HCW9302, to fulfill the requirements for planned clinical development activities in 2024-2025. Preclinical costs in 2022 and 2023 are related to IND-enabling activities required to prepare an IND application to evaluate HCW9302 in a Phase 1b/2 clinical trial. A change in preclinical activities from 2022 to 2023 was the underlying reason for a decline in preclinical expenses. Setup costs were incurred for toxicology studies and other IND-enabling studies in 2022. Costs declined in 2023, as the Company was focused on additional research studies required for the Company’s IND submission.
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General and administrative (G&A) expenses: G&A expenses for the fourth quarters ended December 31, 2022 and 2023 were $3.0 million and $3.6 million, respectively. The $628,910 increase, or 20%, was attributable to an increase in legal expenses related to the Altor/NantCell matter. G&A expenses for the years ended December 31, 2022 and 2023 were $8.3 million and $13.3 million, respectively. The $5.0 million increase, or 60%, was attributable to an increase in legal expenses associated with the Company’s ongoing arbitration with Altor/NantCell. See further discussion of the Altor/NantCell arbitration in "Financial Guidance."
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Reserve for Credit Losses. In the period ended December 31, 2023, the Company recognized a reserve for credit losses related to a $5.3 million interest reserve deposit established in connection with a credit agreement the Company terminated. While the Company is entitled to recover these funds, facts available as of December 31, 2023 indicate it is not probable.
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Net loss: Net loss for the fourth quarters ended December 31, 2022 and 2023 were $5.4 million and $10.7 million, respectively. Net loss for the years ended December 31, 2022 and 2023 was $14.9 million and $25.0 million, respectively.

Financial Guidance

As of December 31, 2023, there was substantial doubt about our ability to continue as a going concern. Since that time, we had successful financings of $12.5 million, for which we received funds or have a legally binding commitment to so as of March 31, 2024. And, we continue with other fundraising efforts that we are targeting to complete in the next three to six months. Under the guidance of Topic 205-40 for going concern assessment, we evaluated whether we mitigated the substantial doubt over our ability to remain a going concern for the next 12 months from the filing date. If no additional financings occur after the filing date, we believe the relevant conditions that brought about substantial doubt can be alleviated if we implement a plan that includes certain adjustments to our strategic and operating plans, such as cutting back on the number of investigative studies and Phase 2 clinical trials we initiate; reducing salaries and other spending, and limiting the amount of cash used to reduce accounts payable, as well as other adjustments to alleviate substantial doubt.

On December 23, 2022, Claimants Altor and NantCell ("Altor/NantCell") filed a complaint against the Company in the U.S. District Court for the Southern District of Florida (the "Court"), alleging claims of misappropriation of trade secrets, tortious interference with contractual relations, inducement of breach of fiduciary duty, and specific performance/injunction for assignment of patents and patent applications, among other claims. That same day, Altor/NantCell also initiated an arbitration against the Company’s CEO and Founder, Dr. Wong, based on early identical allegations and alleging breach of contract, breach of fiduciary duty, and fraudulent concealment, among other claims. The Company moved to compel arbitration and the parties ultimately stipulated to the same. On April 27, 2023, in connection with the Altor/NantCell matter, the Court approved the parties’ stipulation and ordered the parties to arbitration. On May 1, 2023, Altor/NantCell filed a demand against the Company before JAMS. On May 3, 2023, Altor/NantCell dismissed the federal court action without prejudice and the Court ordered the case dismissed without prejudice and closed the case. Altor/NantCell’s proceeding against the Company is now proceeding in arbitration before JAMS, with an arbitration hearing scheduled for May 20, 2024. In addition, on March 26, 2024, Altor/NantCell gave notice that they are filing a complaint (the "Complaint") against the Company in the Chancery Court of the State of Delaware for the contribution of legal fees and expenses advanced to Dr. Wong in connection with the arbitration discussed above. Prior to the filing of the Complaint, Altor/NantCell had previously sought advancement from the Company and the Company agreed to advance 50% of Dr. Wong’s legal fees going forward from December 2023. On January 8, 2024, Altor/NantCell reserved their right to pursue contribution against the Company for 50% of the amount Altor/NantCell sent for advancement of expenses for Dr. Wong. In the Complaint, Altor/NantCell seek 50% of the fees they have already advanced to Dr. Wong, a declaration that the Company has an obligation to contribute 50% of the advancement of Dr. Wong’s expenses including 50% of Dr. Wong’s expenses incurred in connection with the arbitration through final resolution of the matter, and costs and fees in bringing this action. Although adverse decisions (or settlements) may occur in arbitration, it is not possible to reasonably estimate the possible loss or range of loss, if any, associated therewith at this time. As such, no accrual for these matters has been recorded within the Company’s financial statements. The Company incurred significant legal expenses in connection with this matter in the period ended December 31, 2023, and expects to continue to incur material costs and expenses in the first half of 2024.

On April 1, 2024 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and reported financial results for the fourth quarter and full year ended December 31, 2023 (Press release, Xilio Therapeutics, APR 1, 2024, View Source [SID1234641662]).

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"With our recently announced partnership with Gilead for XTX301, our tumor-activated IL-12, and additional financing from existing investors, we believe we are well-positioned to continue to advance our differentiated pipeline of tumor-activated I-O therapies and achieve potential near-term clinical milestones and value-drivers," said René Russo, Pharm.D., president and chief executive officer of Xilio. "Looking ahead, we are focused on rapidly advancing clinical development for XTX301 and XTX101, our tumor-activated, Fc-enhanced anti-CTLA-4, with anticipated clinical data for each of these programs later this year, as well as continuing to leverage our novel research platform to design and develop tumor-activated bispecific and immune cell engager molecules."

Pipeline and Business Updates

XTX101: tumor-activated anti-CTLA-4

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). XTX101 is currently being evaluated in combination with atezolizumab in an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

Xilio today reaffirmed plans to:

● Select a recommended Phase 2 dose for XTX101 in combination with atezolizumab in the second quarter of 2024.
● Subject to the results of the Phase 1 combination dose escalation portion of the trial, initiate the Phase 2 portion of the trial for XTX101 in combination with atezolizumab in patients with microsatellite stable colorectal cancer (MSS CRC) in the third quarter of 2024.
● Report initial Phase 2 data for XTX101 in combination with atezolizumab in approximately 20 patients with MSS CRC in the fourth quarter of 2024 and in approximately 20 additional patients (40 patients total) in the first quarter of 2025.

XTX301: tumor-activated, engineered IL-12

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed, or "hot," state.

In March 2024, Xilio and Gilead Sciences, Inc. (Gilead) announced an exclusive license agreement for Xilio’s tumor-activated IL-12 program, including XTX301. Under the terms of the agreement:

● Xilio is eligible to receive $43.5 million in upfront payments, including a cash payment of $30.0 million and an initial equity investment by Gilead of approximately $13.5 million in Xilio common stock. The initial equity investment closed on March 28, 2024, and the $30.0 million upfront cash payment is payable by Gilead within a specified time period promptly following signing of the license agreement.
● Xilio will be eligible to receive up to $604.0 million in additional contingent payments, including proceeds from up to three additional equity investments by Gilead, a $75.0 million transition fee and specified development, regulatory and sales-based milestones. Xilio will also be eligible to receive tiered royalties ranging from high single digits to mid-teens on annual global net product sales.
● Prior to the potential transition fee, Xilio is eligible to receive up to a total of $29.0 million in additional equity investments and a development milestone payment.
● Xilio will be responsible for conducting clinical development for XTX301 in the ongoing Phase 1 clinical trial through dose expansion. Following the delivery by Xilio of a specified clinical data package for XTX301, Gilead can elect to transition responsibilities for the development and commercialization of XTX301 to Gilead, subject to the terms of the agreement and payment by Gilead of the $75.0 million transition fee. If Gilead elects not to transition responsibilities for development and commercialization of the licensed products and pay the transition fee, then the license agreement will automatically terminate.

For more information, read the press release here.

XTX301 is currently being evaluated in Phase 1 dose escalation in patients with advanced solid tumors.

● In January 2024, Xilio reported encouraging preliminary safety data into the third dose level in the ongoing Phase 1 clinical trial. As of the data cutoff date of January 5, 2024, XTX301 had been administered at doses up to 45 ug/kg, which is nearly 100 times the maximum tolerated dose of recombinant human IL-12, and was generally well-tolerated with no dose-limiting toxicities observed.
● Xilio today reaffirmed plans to report Phase 1 safety, pharmacokinetic and pharmacodynamic data for XTX301 in patients with advanced solid tumors in the fourth quarter of 2024.

XTX202: tumor-activated, engineered IL-2

XTX202 is an investigational tumor-activated, beta-gamma biased IL-2 designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment.

● In March 2024, Xilio announced additional data from its Phase 2 clinical trial evaluating XTX202 in patients with metastatic renal cell carcinoma or unresectable or metastatic melanoma. For more information, read the press release here.
● Together with previously reported data, Xilio believes these additional data further validate the company’s tumor-activated approach and support the broad potential for XTX202 as a combination therapy. Xilio plans to explore strategic opportunities to continue to develop XTX202 in combination with other agents.

Tumor-Activated Bispecific and Immune Cell Engager Programs

In March 2024, Xilio announced plans to focus its research-stage development efforts on tumor-activated bispecifics and immune cell engagers, including tumor-activated cell engagers and tumor-activated effector-enhanced cell engagers.

Preclinical data from the company’s first bispecific program, XTX501, a tumor-activated PD-1/IL-2 bispecific development candidate, will be featured at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2024 in San Diego, California from April 5-10, 2024.

● Presentation title: A tumor-activated PD1/IL2 bispecific molecule, designed to overcome IL-2 receptor-mediated clearance, improve tolerability and stimulate antigen-experienced CD8+ T cells in the tumor microenvironment of murine models
● Session date and time: Sunday, April 7, 2024, at 1:30 pm to 5:00 pm P.T.
● Abstract number: 719
● Poster board number: 5

Corporate Updates

● In March 2024, Xilio announced a private placement equity financing with certain existing accredited investors, including Bain Capital Life Sciences and Rock Springs Capital. Xilio anticipates receiving aggregate gross proceeds from the private placement of approximately $11.3 million, before deducting placement agent fees and expenses payable by the company. The private placement is expected to close on April 2, 2024, subject to the satisfaction of customary closing conditions. Xilio expects to use the proceeds from the private placement to fund working capital and other general corporate purposes.
● In March 2024, Xilio announced plans to implement a strategic portfolio prioritization designed to focus its resources on rapidly advancing clinical development for XTX301 and XTX101 and leveraging the company’s promising research platform to advance differentiated tumor-activated bispecific and immune cell engager molecules. As part of the strategic portfolio reprioritization, Xilio also announced plans to discontinue further investment in XTX202 as a monotherapy and implement an approximately 21% workforce reduction.

Year-End and Fourth Quarter 2023 Financial Results

● Cash Position: Cash and cash equivalents were $44.7 million as of December 31, 2023, compared to $120.4 million as of December 31, 2022.
● Research & Development (R&D) Expenses: R&D expenses were $11.7 million for the quarter ended December 31, 2023, compared to $15.0 million for the quarter ended December 31, 2022. R&D expenses were $52.1 million for the year ended December 31, 2023, compared to $59.2 million for the year ended December 31, 2022. The year-over-year decrease was primarily driven by decreases in manufacturing activities, XTX301 preclinical development activities, XTX101 clinical activities and personnel-related costs. These decreases were partially offset by increases in XTX301 and XTX202 clinical activities.
● General & Administrative (G&A) Expenses: G&A expenses were $6.4 million for the quarter ended December 31, 2023, compared to $8.2 million for the quarter ended December 31, 2022. G&A expenses were $27.0 million for the year ended December 31, 2023, compared to $29.9 million for the year ended December 31, 2022. The year-over-year decrease was primarily driven by decreases in professional and consulting fees, directors’ and officers’ liability insurance and stock-based compensation expenses.

● Net Loss: Net loss was $17.7 million for the quarter ended December 31, 2023, compared to $22.5 million for the quarter ended December 31, 2022. Net loss was $76.4 million for the year ended December 31, 2023, compared to $88.2 million for the year ended December 31, 2022.

Financial Guidance

Based on its current operating plans, Xilio anticipates that its cash and cash equivalents as of December 31, 2023, together with (i) the $30.0 million upfront payment under the license agreement with Gilead, (ii) the approximately $13.5 million in proceeds from the initial private placement with Gilead, which closed on March 28, 2024, and (iii) the approximately $11.3 million in proceeds from the private placement, which is expected to close on April 2, 2024 (subject to customary closing conditions), and after giving effect to (a) one-time costs and anticipated future cost savings associated with Xilio’s strategic portfolio reprioritization and workforce reduction announced in March 2024 and (b) the repayment in the first quarter of 2024 of the outstanding loan balance under Xilio’s loan and security agreement with Pacific Western Bank, will be sufficient to fund its operating expenses and capital expenditure requirements into the second quarter of 2025.

About XTX101 (anti-CTLA-4) and the Phase 1/2 Combination Clinical Trial

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). In the third quarter of 2023, Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate XTX101 in combination with atezolizumab (Tecentriq) in a multi-center, open-label Phase 1/2 clinical trial. Xilio is currently evaluating the safety and tolerability of the combination in patients with advanced solid tumors in the Phase 1 dose escalation portion of the clinical trial. Subject to the results of Phase 1 combination dose escalation, Xilio plans to evaluate the safety and efficacy of the combination in the Phase 2 portion of the clinical trial in patients with microsatellite stable colorectal cancer. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

About XTX301 (IL-12) and the Phase 1 Clinical Trial

XTX301 is an investigational tumor-activated IL-12 designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. In March 2024, Xilio entered into an exclusive license agreement with Gilead Sciences, Inc. for Xilio’s tumor-activated IL-12 program, including XTX301. Xilio is currently evaluating the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors in a first-in-human, multi-center, open-label Phase 1 clinical trial. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

About XTX202 (IL-2) and the Phase 2 Clinical Trial

XTX202 is an investigational tumor-activated, beta-gamma biased IL-2 designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the TME. The Phase 2 clinical trial is a multi-center, open-label trial designed to evaluate the safety and efficacy of XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma who have progressed on standard-of-care treatment. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.