On November 3, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported initial safety, pharmacokinetic (PK), pharmacodynamic (PD) and anti-tumor activity data from its ongoing Phase 1/2 clinical trial evaluating XTX202, an investigational tumor-activated, engineered, beta-gamma IL-2, in late line patients with advanced solid tumors (Press release, Xilio Therapeutics, NOV 3, 2023, View Source [SID1234636905]). The data were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting in San Diego, CA being held on November 1-5, 2023.

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"The newly reported data from our Phase 1/2 clinical trial for XTX202 expands the evidence across our programs supporting clinical validation of our tumor-activated technology. We observed a disease control rate of 50% at higher doses (≥2.8 mg/kg) and 31% across all dose levels in a variety of advanced and IO refractory solid tumors, including cold tumors. Importantly, treatment-related adverse events were primarily Grade 1-2 with no evidence of vascular leak syndrome reported at any dose level, and two patients are continuing on treatment for more than one year, highlighting XTX202’s potential for long-term tolerability at high doses," said Katarina Luptakova, M.D., chief medical officer of Xilio. "In addition, an analysis of an on-treatment biopsy from a patient receiving 2.8 mg/kg of XTX202 demonstrated evidence of activation in the tumor with minimal active drug in peripheral circulation and also suggests that monotherapy doses at or above 2.8 mg/kg are approaching the optimal range to engage CD8+ T effector cell and NK cell expansion while continuing to avoid stimulation of regulatory T cells. Overall, these encouraging data support continued evaluation of XTX202 at a dose of 4.0 mg/kg in our Phase 2 trial of patients with metastatic renal cell carcinoma and unresectable or metastatic melanoma and the exploration of opportunities for combination therapy."

Investigator Dr. Howard Kaufman, M.D., FACS of Massachusetts General Hospital commented, "As opposed to the trademark toxicities associated with recombinant IL-2, the preliminary data from the XTX202 Phase 1/2 clinical trial demonstrate a marked difference in tolerability and the potential for long-term treatment at high doses for XTX202 that has not been possible previously with systemically active IL-2 molecules. These data showcase the importance of concentrating potent IO molecules directly in the tumor microenvironment and offer an encouraging signal for continued investigation of XTX202 monotherapy at high doses along with its broad combination potential with other mechanisms of action where the stimulation of CD8+ T cells and NK cells without expansion of regulatory T cells would be synergistic."

Data from the Ongoing Phase 1/2 Clinical Trial for XTX202

As of a data cutoff date of October 26, 2023, 62 patients with advanced solid tumors had been administered XTX202 in an outpatient setting. Fifty-four (54) patients were treated in Phase 1 monotherapy dose-escalation and dose-expansion at seven dose levels ranging from 0.27 mg/kg to 4 mg/kg administered once every three weeks (Q3W). Eight (8) patients were treated in Phase 2 monotherapy at a dose level of 1.4 mg/kg Q3W.

Patients enrolled in Phase 1 were heavily pre-treated, with 74% of patients previously treated with three or more lines of anti-cancer therapy and 69% of patients previously treated with an immunotherapy. All patients in Phase 2 had been previously treated with an immunotherapy. As of the data cutoff date, 20 patients were continuing treatment with XTX202 across the Phase 1/2 trial.

Preliminary Safety Data

Across all dose levels administered in the Phase 1/2 trial, 62 patients were evaluable for safety.

● No signs or symptoms of vascular leak syndrome were reported by investigators through the 4.0 mg/kg dose.
● XTX202 was generally well-tolerated. Treatment-related adverse events (TRAE) were primarily Grade 1 or 2, and no patients discontinued treatment due to a TRAE. Higher grade TRAEs were primarily asymptomatic laboratory abnormalities, and no Grade 5 TRAEs were reported by investigators.
● The most common TRAEs (≥10% incidence) of any grade reported by investigators across all dose levels were: fatigue (19%, no grade ≥3); pyrexia (18%, no grade ≥3); chills (16%, 2% grade 3); and lymphocyte count decreased (15%, 8% grade 3-4). Grade 3 TRAEs reported in one patient each (2%) were: diarrhea/colitis; myalgia; hypoxia; lymphopenia; and aspartate transferase (AST)/alanine transaminase (ALT) increased. Investigators reported two Grade 4 TRAEs of lymphocyte count decreased/lymphopenia, which were both transient (<3 days) and resolved without intervention, with both patients able to continue on treatment.
● Across all dose levels, only two patients (3%) had a dose reduction due to a TRAE, and only one dose-limiting toxicity was observed, which was a reversible and transient (<5 days) Grade 3 elevation of AST and ALT at the 1 mg/kg dose.
Preliminary Anti-Tumor Activity

Across all dose levels administered in the Phase 1/2 trial, 42 patients were evaluable for anti-tumor activity. Of these response-evaluable patients, 27 patients were treated at dose levels of 1.4 mg/kg or higher, including six patients treated at the 2.8 mg/kg dose level or higher.

● Data demonstrated evidence of a dose-dependent increase in disease control rate (DCR). Among the 42 response-evaluable patients treated across all dose levels, investigators reported stable disease (SD) of at least 9-weeks duration in 13 patients (31% DCR) across a range of solid tumors, including cold tumors: melanoma (n=3); renal cell carcinoma (RCC) (n=2); non-small cell lung cancer (n=2); colorectal cancer (n=2); and myoepithelial carcinoma, vaginal cancer, testicular cancer and squamous penile cancer (n=1 each). Among the six response-evaluable patients treated at the 2.8 mg/kg dose level or higher, investigators reported SD of at least 9-weeks duration in three patients (50% DCR).
● In addition, two patients were ongoing on treatment for more than one year as of the data cutoff date, including a treatment-refractory microsatellite stable colorectal cancer (MSS CRC) patient and an RCC patient, suggesting XTX202 was well-tolerated with repeated, long-term dosing in these patients.
Preliminary PK and PD Data

Preliminary PK analysis demonstrated limited XTX202 activation in peripheral circulation, including:

● Dose-proportional exposure for XTX202 with minimal levels of unmasked XTX202 detected in peripheral circulation that were consistent across dose levels.
● Approximately 15% activated XTX202 in the tumor based on an analysis of an on-treatment patient biopsy for a patient treated with XTX202 at the 2.8 mg/kg dose level as compared to <1% activated XTX202 in plasma across patients treated with XTX202 at the 2.8 mg/kg dose level for whom PK analysis was available. These data along with non-clinical pharmacology data suggest 2.8 mg/kg or higher monotherapy doses of XTX202 are approaching the optimal range to activate CD8+ effector T cells and natural killer (NK) cells in the tumor.
Consistent with IL-2 beta-gamma biology, preliminary PD analysis of four available on-treatment tumor samples showed an average increase >200% of CD8+ effector T cells in the tumor as compared to pre-treatment biopsies.

Poster Presentation

A copy of Xilio’s data presentation from the SITC (Free SITC Whitepaper) Annual Meeting for XTX202 is available in the "Our Approach—Publications and Presentations" section of the company’s website at www.xiliotx.com.

Clinical Development Plans for XTX202

XTX202 recently cleared dose level seven (4.0 mg/kg) in Phase 1 monotherapy dose-escalation, and Xilio recently opened enrollment at a second dose level of 4.0 mg/kg in the ongoing Phase 2 monotherapy trial for XTX202. Based on the initial monotherapy data for XTX202, Xilio also plans to explore opportunities for strategic partnerships to evaluate XTX202 as a combination therapy.

Key Upcoming Milestones

As previously reported, Xilio anticipates achieving the following milestones in 2023:

● Activate clinical trial sites for the Phase 1 dose escalation portion of the clinical trial evaluating XTX101, a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab in the fourth quarter of 2023
● Report preliminary Phase 1 safety data for XTX301, a tumor-activated, engineered IL-12, into the third dose level in the fourth quarter of 2023
In addition, subject to obtaining sufficient additional capital, Xilio reported plans to:

● Complete Phase 1 combination dose escalation and select a recommended Phase 2 dose for XTX101 in combination with atezolizumab in the second quarter of 2024
● Subject to the results of Phase 1 combination dose escalation, initiate a Phase 2 trial for XTX101 in combination with atezolizumab in patients with 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
● Report Phase 2 monotherapy data for XTX202 in approximately 20 patients treated at the 4.0 mg/kg dose with metastatic RCC or unresectable or metastatic melanoma in the second quarter of 2024
● Report Phase 1 safety and PK/PD data for XTX301 in advanced solid tumors in the second half of 2024
Conference Call Information

As previously announced, Xilio Therapeutics will host a live conference call and webcast Monday, November 6, 2023 at 8:00 a.m. ET to review progress across its pipeline of tumor-activated molecules, including the Phase 1/2 clinical data presented for XTX202 at the SITC (Free SITC Whitepaper) Annual Meeting. The webcast may be accessed by clicking here. The webcast of the conference call will also be available under "Events and Presentations" in the Investors & Media section of the Xilio Therapeutics website at View Source The archived webcast will become available on the Xilio Therapeutics website approximately two hours after the conference call and will be available for 30 days following the call.

About XTX202 and the Phase 1/2 Clinical Trials

XTX202 is an investigational tumor-activated beta-gamma biased, engineered IL-2 molecule 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 (TME). The Phase 1 clinical trial for XTX202 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 2 clinical trial for XTX202 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.

On November 3, 2023 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported data from multiple preclinical-stage XmAb programs at the 38th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in San Diego (Press release, Xencor, NOV 3, 2023, View Source [SID1234636904]).

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"Xencor aims to stay on the leading edge of molecular engineering, using and improving upon our XmAb technologies to create molecules with enhanced functionality or new therapeutic mechanisms. At SITC (Free SITC Whitepaper), we are presenting new preclinical data from two research-stage programs—engineered, decoy-resistant IL18-Fc fusions and our multi-valent NK cell engagers targeted to MICA and MICB, which are tumor antigens upregulated in the tumor microenvironment," said John Desjarlais, Ph.D., executive vice president and chief scientific officer at Xencor. "Later this year, we expect to submit an investigational new drug application for XmAb541, an XmAb 2+1 format CLDN6 x CD3 bispecific antibody that we are developing for patients with ovarian cancer and other tumor types. We are also developing additional CD3 and CD28 T cell engaging bispecific antibodies against solid tumor targets."

Posters will be available in the poster hall and virtually to registrants of the SITC (Free SITC Whitepaper) Annual Meeting. In the poster hall, odd-numbered posters will be displayed on Friday, November 3, and even-numbered posters will be displayed on Saturday, November 4. Xencor’s posters will be archived under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com.

Clinical Trials in Progress

Abstract 764, "A Phase 1, first-in-human (FIH), open-label, dose-finding and expansion study of XmAb808, a B7H3 x CD28 bispecific antibody, in combination with pembrolizumab in patients with advanced solid tumors"

Xencor is conducting a Phase 1 study of XmAb808 in patients with advanced solid tumors. XmAb808 is a tumor-selective, co-stimulatory XmAb 2+1 bispecific antibody designed to bind to the broadly expressed tumor antigen B7-H3 and selectively to the CD28 T-cell co-receptor only when bound to tumor cells, which was demonstrated in vitro. Strong potentiation of checkpoint and CD3 cytotoxic activity was also observed in vivo. XmAb808 is a wholly owned Xencor program.

The clinical trials in progress poster reviews the design of XmAb808 and the rationale of using CD28 bispecific antibodies to expand the utility of checkpoint blockade and CD3 T cell engagers. The poster also provides study objectives, key eligibility criteria and study schema.

Preclinical Programs

Abstract 1060, "Optimally engineered IL18-Fc fusion proteins balance potency and pharmacokinetics to promote strong anti-tumor activity"

IL-18 is a proinflammatory cytokine that modulates both the innate and adaptive immune responses. Preclinical studies of IL-18 have demonstrated its anti-tumor activity, including synergy with immune checkpoint inhibitors and CAR-T therapies. In contrast with other potent cytokines, IL-18 has been well tolerated in clinical trials but demonstrated a lack of efficacy despite heavy dosing. IL-18 induces a negative feedback loop with its high affinity natural inhibitor, IL18BP, which was upregulated in early phase clinical studies and may have limited IL-18’s clinical performance.

Xencor engineered stabilized, potency-modulated IL-18 cytokines fused to an XmAb heterodimeric Fc domain with Xtend Fc technology for longer half-life (IL18-Fc). In addition, Xencor engineered bispecific IL18-Fc cytokines targeted to PD-1, a checkpoint receptor on T cells. Importantly, these molecules were engineered to avoid binding IL18BP.

Xencor’s IL18-Fc fusions and PD1 x IL18-Fc bispecific inhibited tumor growth in a dose- and potency-dependent manner, outperforming a wild-type IL18-Fc fusion, in vivo. Further preclinical studies of the engineered IL18-Fc fusions demonstrated pharmacodynamic profiles similar to wild-type IL18-Fc. Notably, a set of surviving tumor-engrafted mice, which had previously received engineered IL18-Fc fusions, had no tumor growth upon rechallenge.

Abstract 1193, "Synergistic targeting of multiple activating pathways with Natural Killer cell Engagers"

Xencor’s XmAb natural killer cell engagers (NKEs) are multifunctional antibodies that target multiple activating receptors on the surface of NK cells and bind to tumor-associated antigens.

MICA and MICB (MICA/B) are stress-induced tumor antigens expressed in a range of cancers. MICA/B antigens are recognized by NKG2D, an activating receptor on NK and CD8+ T cells. While membrane-bound, MICA/B is immuno-stimulatory; however, the cleaved and soluble form, found in the tumor microenvironment, prevents NKG2D from recognizing tumor cells. Xencor engineered anti-MICA/B antibodies with enhanced effector function in order to block the cleavage of MICA/B antigens and promote NK cell engagement. These antibodies increased MICA/B membrane surface density and led to tumor cell killing with MICA/B binding to NKG2D on immune cells. To enhance the anti-tumor activity, Xencor engineered multi-specific NK cell-engaging antibodies that simultaneously target MICA/B antigens and an orthogonal activating receptor on NK cells, NKp46. These multi-specific NK cell-engaging antibodies demonstrated enhanced functional activity compared to the antibodies targeting only MICA/B.

On November 3, 2023 Werewolf Therapeutics, Inc. (the "Company" or "Werewolf") (Nasdaq: HOWL), an innovative biopharmaceutical company pioneering the development of conditionally activated therapeutics engineered to stimulate the body’s immune system for the treatment of cancer, reported preliminary first-in-human clinical data from initial monotherapy dose-escalation cohorts in the Company’s lead clinical program, WTX-124×2101 (Press release, Werewolf Therapeutics, NOV 3, 2023, View Source [SID1234636903]). This clinical program is an ongoing, multi-center Phase 1/1b clinical trial of WTX-124, Werewolf’s interleukin 2 (IL-2) INDUKINE molecule, in patients with advanced or metastatic solid tumors. The preliminary data will be presented today at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting in San Diego, California.

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Study WTX-124×2101 is evaluating WTX-124 as a monotherapy and in combination with pembrolizumab in patients with immunotherapy sensitive advanced or metastatic solid tumors who have failed standard of care treatment, including checkpoint inhibitor therapy. The preliminary data include data collected as of October 18, 2023, from 16 heavily pretreated patients from the first four monotherapy dose escalation cohorts (1, 3, 6, 12 mg). The preliminary data established proof of mechanism for WTX-124 and proof of concept for Werewolf’s INDUKINE design.

"We are encouraged by these preliminary data demonstrating that WTX-124 was generally well tolerated while delivering a wild-type IL-2 to the tumor microenvironment and eliciting monotherapy biomarker and clinical activity including two patients with ongoing unconfirmed partial responses in the 12mg cohort," said Daniel J. Hicklin, Ph.D., President and Chief Executive Officer of Werewolf. "We look forward to sharing additional data to inform our recommended dose to proceed into monotherapy expansion arms in the first half of 2024."

The preliminary data include assessments of safety and tolerability, pharmacokinetics, relevant biomarkers and preliminary antitumor activity. Data as of the October 18, 2023, cutoff date are summarized as follows:

WTX-124 was generally well-tolerated at all doses tested up to and including 12 mg in the outpatient setting.
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All treatment-emergent adverse events (TEAEs) were Grade 1 or Grade 2, and arthralgias and fatigue were the most common TEAEs. Vascular leak syndrome was not observed, and there were no dose limiting toxicities, treatment-related serious adverse events (SAEs) or treatment-related study discontinuations.

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WTX-124 was delivered intravenously once every two weeks (Q2W).

WTX-124 showed expected pharmacokinetics with evidence of wide therapeutic index allowing for continued dose escalation.

WTX-124 demonstrated both translational biomarker activity and early evidence of monotherapy antitumor activity at 6 mg and 12 mg doses.

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CD8+ T and NK cell proliferation and activation in the tumor microenvironment and immune cell gene expression changes were seen at 6 mg and 12 mg dose levels.
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Among five patients treated at 12 mg, one patient achieved an unconfirmed partial response (uPR), one patient had a restaging scan that was consistent with a partial response as of November 1, 2023, and one other showed evidence of anti-tumor activity.

"IL-2 is a well-validated cytokine, but the challenges associated with administering high-dose IL-2 have limited its use. Next-generation approaches have not been successful to date in demonstrating monotherapy activity at well-tolerated doses," said Randi Isaacs, M.D., Chief Medical Officer of Werewolf. "Although still early in the trial, today’s presentation at SITC (Free SITC Whitepaper) of preliminary data from monotherapy dose escalation highlights WTX-124’s potential to deliver this important mechanism with limited toxicity and to provide another therapeutic option to cancer patients."

Dose escalation is ongoing in the monotherapy and combination therapy arms of the trial with additional data from monotherapy dose-escalation cohorts informing declaration of recommended dose for expansion (RDE) and opening of the monotherapy expansion arms expected in the first half of 2024.

In addition, five preclinical posters further supporting the INDUKINE hypothesis, WTX-124 properties, and other INDUKINE molecules are being presented at the meeting, including:

Title: PK/RO Modeling of WTX-124, a Tumor-Activated IL-2 Prodrug, Highlights the Potential for a Substantially Improved Therapeutic Index Compared to Other IL-2 Molecules (Abstract #1074)

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Plasma and tumor data from mice were used to perform pharmacodynamic and receptor occupancy modeling to predict IL-2 receptor occupancy on peripheral lymphocytes and tumor infiltrating lymphocytes (TILs) suggesting WTX-124 has a substantially improved, best-in-class therapeutic index as compared to other IL-2 molecules investigated, including a half-life extended non-alpha IL-2 and a non-alpha IL-2 tumor-activated prodrug.

Title: Optimal Antitumor Immunity Triggered by WTX-124, a Clinical Stage Conditionally Activated INDUKINETM Molecule that Releases Fully Potent IL-2 in the Tumor Microenvironment (Abstract #1058)
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WTX-124 generated robust anti-tumor activity in a MC38 tumor bearing mouse model and promoted the expansion and activation of tumor specific CD8+ T cells as compared to a variant Non-Alpha IL-2 containing INDUKINE molecule which failed to generate anti-tumor activity, to drive tumor specific CD8+ T cell expansion, or to activate tumor infiltrating immune cells even when dosed up to 28 times higher than the active dose of WTX-124. In addition, while both molecules protected tumor infiltrating CD8+ T cells from exhaustion, only treatment with WTX-124 was able to induce an effector phenotype in tumor specific CD8+ T cells and drive clustering of CD8+ T cells with CD103+ cross presenting dendritic cells within the tumor.

Title: Spatial Analysis of Tumor Infiltrating Lymphocyte Populations in Syngeneic Mouse Tumor Models After Treatment with IL-12 (mWTX-330) and IL-2 (WTX-124) INDUKINETM Molecules (Abstract #1059)
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Combination treatment with WTX-124 and alpha PD-1 generated robust anti-tumor activity in a CT26 model resulting in widespread tumor infiltration by CD8+ T cells driving immune activation in the tumor microenvironment. In addition, detection of structured and unstructured lymphoid aggregates, including the clustering of various adaptive and innate immune cells within the tumor microenvironment suggests a zone of cytotoxic cell education within the tumor microenvironment.

Title: The Combination of ACT and INDUKINETM Therapy Leads to Improved Antitumor Immunity in Solid Tumors (Abstract # 252)

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Systemic WTX-124 was shown to preferentially expand CD4 CAR T cells while WTX-330 expanded CD8 CAR T cells, demonstrating that the administration of INDUKINE proteins with adoptive cell therapy could reinvigorate donor cell function leading to improved immunity, engraftment and long-term responses in solid tumors.

Title: Development of WTX-712, a Conditionally Activated IL-21 INDUKINETM Molecule for the Treatment of Cancer (Abstract # 1075)

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WTX-712 was shown to be peripherally inactive in preclinical studies, releasing IL-21 selectively within the tumor microenvironment while driving CD8+ T cell polyfunctionality and promoting immune cell interactions. In addition, WTX-712 demonstrated enhanced activity when combined with immune checkpoint inhibitors, blocking PD-1/PD-L1 or CTLA-4 pathways, indicating further evaluation of WTX-712 is warranted.

The posters will be available on the ‘Scientific Resources’ section of Werewolf Therapeutics website at View Source

Conference Call Information:

Management will host a call to review the preliminary data today, November 3, at 8:30 AM ET. Details for the call can be found here and at View Source

On November 3, 2023 TG Therapeutics, Inc. (NASDAQ: TGTX) reported that Michael S. Weiss, the Company’s Chairman and Chief Executive Officer, reported that it will participate in the 5th Annual Guggenheim Inflammation, Neurology & Immunology (INI) Conference, being held at the JW Marriott Essex House, in New York City on November 6 -7, 2023 (Press release, TG Therapeutics, NOV 3, 2023, View Source [SID1234636902]). The fireside chat is scheduled to take place on Monday, November 6, 2023, at 3:10 PM ET.

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A live webcast of the fireside chat will be available on the Events page, located within the Investors & Media section, of the Company’s website at View Source

On November 3, 2023 Tallac Therapeutics, Inc., a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported the first presentation of TAC-001 Phase 1 clinical safety and efficacy data in solid tumor patients (Press release, Tallac Therapeutics, NOV 3, 2023, View Source [SID1234636901]). TAC-001 is an investigational, systemically delivered, TRAAC molecule comprised of a potent TLR9 Agonist conjugated to a CD22 antibody, designed to selectively activate B cells to drive an anti-tumor immune response.

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The findings presented in the TAC-001 poster "INCLINE-101: Preliminary Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of TAC-001 (TLR9 Agonist Conjugated to a CD22 mAb) in Patients With Advanced or Metastatic Solid Tumors" demonstrate that single-agent TAC-001 (0.1 to 3 mg/kg) given systemically every 2 weeks is well tolerated, demonstrates pharmacodynamic activity consistent with its proposed MOA and resulted in preliminary clinical activity with patients achieving durable stable disease (≥6 months) and partial response per RECIST v1.1.

"These TAC-001 clinical data provide evidence that systemic administration of a TLR9 immune agonist targeting and activating B cells is generally well tolerated and induces immune activation consistent with preclinical studies. We also observed single-agent clinical benefit in late-stage metastatic cancer patients which supports the use of this novel agent for treating cancer," said Kevin N. Heller, M.D., Chief Medical Officer at Tallac Therapeutics. "The pharmacodynamic biomarker data collected from these patients is highly encouraging. We look forward to continuing TAC-001 monotherapy dose escalation and further evaluating activity in selected patient populations. We would like to thank the participants and their families for their participation in our study."

Additionally, the Company presented preclinical data in the poster titled "TAC-003, a TLR9 Agonist Antibody Conjugate for Targeted Immunotherapy of Nectin-4 Expressing Tumors" that demonstrate TAC-003 induces robust immune cell activation, leading to innate and adaptive immunity against Nectin-4 positive cancers and potent single-agent anti-tumor activity. TAC-003 single agent treatment results in durable curative responses in models with a range of low to high Nectin-4 expression, including anti-PD-1 refractory tumors, with improved efficacy compared to enfortumab vedotin. TAC-003 has completed pre-clinical testing, including exploratory toxicological studies in cynomolgus monkeys, and has been selected as the Company’s third clinical candidate.

"We are excited to see these initial clinical data with TAC-001, the first program from Tallac’s TRAAC platform," said Dr. Hong I. Wan, president, CEO and co-founder of Tallac Therapeutics. "As we advance the TAC-001 program, we are also progressing our pipeline of immunotherapy candidates. TAC-003 represents a differentiated asset with potential to address unmet medical needs in multiple cancer types."

TLR9 agonists are a class of immunotherapy that generate both innate and adaptive immune response, which may produce more robust and durable anti-cancer immunity to help overcome resistance to standard-of-care oncology treatments. TLR9 agonists have demonstrated clinical activity in melanoma patients when administered intratumorally. Tallac Therapeutic’s TRAAC platform is designed to deliver a potent and differentiated TLR9 agonist (T-CpG) for targeted immune activation via systemic administration.

About TAC-001 (CD22 TRAAC)
TAC-001 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a potent toll-like receptor 9 agonist (T-CpG) conjugated to an antibody against CD22, a receptor restricted to B cells, including tumor-infiltrating B cells. TAC-001 is designed to systemically deliver T-CpG to B cells by binding to CD22, leading to internalization of TAC-001, TLR9 signaling, B cell activation and a cascade of immune reactions. Preclinical studies demonstrate that the innate and adaptive immune responses triggered by TAC-001 lead to potent anti-tumor activity. TAC-001 is being developed for the treatment of solid tumors and is currently in a Phase 1/2 Study in cancer patients (NCT05399654)

About TAC-003 (Nectin-4 TRAAC)
TAC-003 is a Toll-like Receptor Agonist Antibody Conjugate (TRAAC) comprised of a T-CpG conjugated to a novel Nectin-4-targeting antibody for systemic administration and TME delivery of a potent TLR9 agonist. Nectin-4 is a cancer associated antigen over-expressed in many solid tumor types with limited expression in normal tissues. Additionally, Nectin-4 over-expression correlates with poor prognosis. Preclinical data demonstrate that TAC-003 triggers TLR9 signaling, induces myeloid and dendritic cell activation, phagocytosis, cytokine production and lymphocyte activation, resulting in potent single-agent anti-tumor efficacy.