Xencor Announces XmAb Drug Candidates in Autoimmune Disease with Near-Term Clinical Plans and Shares Clinical Progress in Early-Stage Oncology Programs

Rhea-AI Summary

Xencor, Inc. (NASDAQ: XNCR) announced four new XmAb® programs for treating autoimmune diseases and provided updates on early-stage oncology programs. Key highlights include:

1. XmAb942: Phase 1 study for IBD to start Q4 2024, with data expected H1 2025.
2. Plamotamab (CD20 x CD3) and XmAb657 (CD19 x CD3): To be evaluated for autoimmune diseases, with studies starting in 2025.
3. XmAb819 (ENPP3 x CD3): Showing encouraging clinical activity in advanced clear cell renal cell carcinoma.
4. XmAb808 (B7-H3 x CD28): Demonstrating PSA declines in metastatic castration-resistant prostate cancer patients.

The company aims to leverage its protein engineering strengths to increase clinical success opportunities.

Positive

• XmAb819 shows initial encouraging clinical activity including RECIST responses in advanced clear cell renal cell carcinoma
• XmAb808 demonstrates PSA declines in metastatic castration-resistant prostate cancer patients
• Plamotamab completed Phase 1 study in hematologic cancers with favorable tolerability and comparable preliminary efficacy
• XmAb657 showed deep B-cell reduction of over 99.98% in non-human primate studies
• XmAb942 demonstrates potentially class-leading potency for IBD treatment

Negative

• No maximum tolerated dose reached for XmAb819, requiring continued dose escalation
• Cytokine release syndrome observed in XmAb819 trials, though manageable

Insights

Financial Analyst

Xencor's announcement of new drug candidates and clinical progress is moderately positive for investors. The company is expanding its pipeline in autoimmune diseases, a potentially lucrative market. The planned initiation of multiple clinical trials in 2024 and 2025 indicates a strong development pipeline, which could lead to future revenue streams if successful. However, these are early-stage programs and the road to market is long and uncertain.

The encouraging initial results from XmAb819 in renal cell carcinoma and XmAb808 in prostate cancer are promising, but it's too early to determine their commercial potential. The company's focus on leveraging its XmAb platform across multiple indications demonstrates a strategic approach to R&D, potentially increasing the odds of clinical and commercial success.

Investors should note that while the pipeline expansion is positive, it will likely lead to increased R&D expenses in the near term. The company's cash burn rate may accelerate, which could impact its financial position. Overall, this news suggests Xencor is making progress, but significant revenue-generating products are still years away.

Medical Research Analyst

Xencor's pipeline expansion into autoimmune diseases is a strategic move that capitalizes on the growing understanding of B-cell and T-cell biology in these conditions. The company's approach of repurposing its oncology assets (plamotamab and XmAb657) for autoimmune diseases is innovative and could potentially accelerate development timelines.

The initial encouraging results for XmAb819 in renal cell carcinoma are noteworthy, particularly the RECIST responses and extended treatment duration for some patients. This suggests the drug may have meaningful clinical activity. Similarly, the PSA declines observed with XmAb808 in prostate cancer patients during monotherapy are intriguing, though more data is needed to confirm efficacy.

The development of XmAb942, a high-affinity anti-TL1A antibody, for inflammatory bowel diseases is particularly interesting. TL1A is a validated target in IBD and if XmAb942 can demonstrate superior efficacy or a better dosing regimen compared to competitors, it could capture significant market share. The potential 8-12 week dosing regimen could offer a competitive advantage in patient convenience.

Market Research Analyst

Xencor's expansion into autoimmune diseases positions the company to tap into a lucrative and growing market. The global autoimmune disease therapeutics market is projected to reach $153.32 billion by 2025, with a CAGR of 4.1%. This move diversifies Xencor's portfolio beyond oncology, potentially reducing risk.

The company's focus on multi-drug resistant rheumatoid arthritis (MDR-RA) with plamotamab addresses an unmet medical need. The RA market is highly competitive, but there's still demand for effective treatments for patients who don't respond to current therapies. If successful, this could carve out a valuable niche for Xencor.

In the inflammatory bowel disease space, Xencor's XmAb942 and TL1A x IL-23 bispecific antibody will face stiff competition from established players. However, the potential for extended dosing intervals and dual-targeting approach could differentiate these products. The IBD market is expected to reach $31.4 billion by 2030, offering significant opportunity if Xencor can capture even a small market share.

Investors should note that while these programs expand Xencor's potential market reach, they also increase the company's risk profile due to the complexities and high failure rates in autoimmune disease drug development.

– Phase 1 healthy volunteer study of half-life extended anti-TL1A antibody XmAb942 to dose first subject in Q4 2024, with data anticipated in the first half of 2025 –

– XmAb® T-cell engagers plamotamab (CD20 x CD3) and XmAb657 (CD19 x CD3) to be evaluated in autoimmune diseases, with respective Phase 1b/2a and Phase 1 studies to initiate in 2025 –

– Ongoing Phase 1 dose escalation of XmAb819 (ENPP3 x CD3) in advanced clear cell renal cell carcinoma shows initial encouraging clinical activity including RECIST responses –

– Management hosting webcast and conference call at 8:00 a.m. ET / 5:00 a.m. PT today –

PASADENA, Calif.--(BUSINESS WIRE)-- Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, today announced four new XmAb® programs in development for the treatment of patients with autoimmune diseases and provided updates from dose-escalation studies evaluating its first-in-class oncology programs, including XmAb819 (ENPP3 x CD3) in patients with advanced clear cell renal cell carcinoma and XmAb808 (B7-H3 x CD28) in patients with advanced solid tumors.

“Xencor’s clinical pipeline of XmAb bispecific T-cell engagers and newly announced autoimmune programs have multiple near-term milestones and offer a balance of opportunities to deliver novel treatment options that could potentially make a real difference in patients’ lives. The foundation of our portfolio is world-class protein engineering, using our XmAb platforms to potentially solve complex engineering problems and rationally build drug candidates that address specific clinical opportunities,” said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. “Our goal is clear—fully leverage our protein engineering strengths and reduce exposure to biological uncertainties to increase our overall opportunities for clinical success.”

Clinical Progress Updates in Early-Stage Oncology Programs: XmAb819 (ENPP3 x CD3) and XmAb808 (B7-H3 x CD28)

XmAb819: ENPP3 x CD3 bispecific T-cell engager in Phase 1 dose escalation for patients with advanced clear-cell renal cell carcinoma (ccRCC)

XmAb819 is designed to engage the immune system, activating T cells for highly potent and targeted killing of tumor cells expressing ENPP3, an antigen highly expressed on kidney cancers. Xencor’s XmAb 2+1 multivalent format used in XmAb819 enables greater selectivity of ENPP3-expressing tumor cells compared to normal cells, which express lower levels of ENPP3.

• Clinical update: Initial evidence of anti-tumor activity has been observed in recent dose-escalation cohorts in the ongoing Phase 1 study, including RECIST responses, and the duration of treatment for several patients in earlier dose cohorts has extended beyond one year. Cytokine release syndrome remains manageable, and the tolerability profile from recent dose cohorts, including no maximum tolerated dose being reached, supports continued dose escalation toward target dose levels.
• Guidance: The Company continues to anticipate reaching target dose levels by year end and plans to provide a clinical update around initiation of the first dose expansion cohort during the first half of 2025.

XmAb808: B7-H3 x CD28 bispecific T-cell engager in Phase 1 dose escalation in advanced solid tumors

XmAb808 is a tumor-selective, co-stimulatory CD28 bispecific antibody that binds to the broadly expressed tumor antigen B7-H3 and is constructed with the XmAb 2+1 format. Co-stimulation is required for T cells to achieve full activation, and targeted CD28 bispecific antibodies may provide conditional co-stimulation of T cells when the antibodies are bound to tumor cells.

• Clinical update: The majority of patients enrolled into the ongoing Phase 1 dose-escalation study are men with metastatic castration-resistant prostate cancer (mCRPC). In this group of patients, prostate specific antigen (PSA) declines have been observed during the four-week monotherapy safety run-in period. Tolerability from recent dose cohorts remains supportive of continued dose escalation in combination with pembrolizumab.
• Guidance: The Company continues to anticipate reaching target dose levels by year end and plans to provide a clinical update around initiation of dose expansion cohorts during the first half of 2025.

XmAb Drug Candidates for the Treatment of Patients with Autoimmune and Inflammatory Diseases and Planned Clinical Studies: Plamotamab (CD20 x CD3), XmAb657 (CD19 x CD3), XmAb942 (Xtend™ TL1A) and the XmAb TL1A x IL-23 Program

Plamotamab: CD20 x CD3 bispecific T-cell engager to be evaluated in patients with multi-drug resistant rheumatoid arthritis (MDR-RA), with Phase 1b/2a study anticipated to initiate in the first half of 2025

Xencor plans to initiate a Phase 1b/2a proof-of-concept study for plamotamab in MDR-RA in the first half of 2025. The Phase 1b portion of the study will select a priming and step-up dose regimen based on the regimen established in oncology, and will assess the initial safety, efficacy, and biomarkers of plamotamab in patients with MDR-RA. The selected dose regimen will then be evaluated in the randomized Phase 2a portion, with efficacy determined at week 24.

Xencor previously completed a Phase 1 clinical study of plamotamab in hematologic cancers, completing enrollment in late 2023. Results from the study showed favorable tolerability and comparable preliminary efficacy data, when cross compared to results from studies of a competitor molecule within the class, with similar patient baseline characteristics. Based on these clinical outcomes, significant B-cell depletion observed in preclinical studies, and the emergent biology supportive of B-cell targeted T cell engagers for the treatment of patients with autoimmune diseases, Xencor plans to evaluate plamotamab in MDR-RA, in which patients progressed through two prior lines of therapy.

XmAb657: Rationally designed CD19 x CD3 bispecific T-cell engager for patients with autoimmune diseases, with first-in-human Phase 1 study anticipated to initiate in the second half of 2025

Xencor has leveraged its XmAb protein engineering platforms to create XmAb657, a potent, potentially long-acting CD19 x CD3 bispecific antibody, utilizing the XmAb 2+1 bispecific antibody format and Xtend™ Fc technology. In non-human primate studies, a single dose of XmAb657 deeply reduced B cells by over 99.98% in the peripheral compartment, bone marrow and lymph nodes, which was sustained for at least 28 days. Half-life was estimated to be 15 days, which indicates a potential for durable B-cell depletion in clinical studies. XmAb657 was well tolerated preclinically, with no clinical signs of cytokine release syndrome. Xencor plans to initiate a first-in-human study during the second half of 2025.

XmAb942: A novel high-affinity anti-TL1A antibody designed for extended half-life, under development for the treatment of inflammatory bowel diseases (IBD), with first-in-human Phase 1 study anticipated to initiate in the fourth quarter 2024

XmAb942 is a monospecific anti-TL1A antibody, utilizing Xencor’s Xtend Fc domain and proprietary Fc silencing technology, with potentially class-leading potency, and is under development for patients with IBD. The two most common forms of IBD are Crohn’s disease and ulcerative colitis. Half-life preclinically was greater than 22 days, potentially supporting an 8- to 12-week dosing regimen in humans. An abstract with preclinical characterization was accepted for presentation at the United Europe Gastroenterology Week (UEGW) in Vienna, Austria on Tuesday, October 15. Xencor anticipates dosing the first subject in a first-in-human, single-ascending dose study of XmAb942 in the fourth quarter of 2024, with interim data during the first half of 2025.

XmAb TL1A x IL-23 Program: Potential first-in-class bispecific antibody to combine two validated biological pathways of interest into one drug candidate for the treatment of IBD, leveraging Xencor’s world-class protein engineering

An expertly engineered XmAb TL1A x IL-23p19 bispecific antibody could potentially provide dual targeting of important inflammatory pathways for autoimmune and inflammatory disease, while avoiding the complexities of dosing and formulary access for two separate TL1A and IL23 targeted drugs. Xencor anticipates initiating first-in-human studies during 2026.

Conference Call and Webcast

Xencor will host a conference call and webcast today at 8:00 a.m. ET (5:00 a.m. PT) to review the topics outlined in this news release.

The live webcast may be accessed through “Events & Presentations” in the Investors section of the Company’s website, located at investors.xencor.com. Telephone participants may register to receive a dial-in number and unique passcode that can be used to access the conference call. A recording will be available for at least 30 days.

About Xencor

Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and other serious diseases. More than 20 candidates engineered with Xencor's XmAb® technology are in clinical development, and multiple XmAb medicines are marketed by partners. Xencor's XmAb engineering technology enables small changes to a protein’s structure that result in new mechanisms of therapeutic action. For more information, please visit www.xencor.com.

Forward-Looking Statements

Certain statements contained in this press release may constitute forward-looking statements within the meaning of applicable securities laws. Forward-looking statements include statements that are not purely statements of historical fact, and can generally be identified by the use of words such as “potential,” “can,” “will,” “plan,” “may,” “could,” “would,” “expect,” “anticipate,” “seek,” “look forward,” “believe,” “committed,” “investigational,” and similar terms, or by express or implied discussions relating to Xencor’s business, including, but not limited to, statements regarding expectations for clinical progress, planned presentations of clinical data, new XmAb candidates and programs, planned and in process clinical trials, the quotations from Xencor's president and chief executive officer, and other statements that are not purely statements of historical fact. Such statements are made on the basis of the current beliefs, expectations, and assumptions of the management of Xencor and are subject to significant known and unknown risks, uncertainties and other factors that may cause actual results, performance or achievements and the timing of events to be materially different from those implied by such statements, and therefore these statements should not be read as guarantees of future performance or results. Such risks include, without limitation, the risks associated with the process of discovering, developing, manufacturing and commercializing drugs that are safe and effective for use as human therapeutics and other risks, including the ability of publicly disclosed preliminary clinical trial data to support continued clinical development and regulatory approval for specific treatments, in each case as described in Xencor's public securities filings. For a discussion of these and other factors, please refer to Xencor's annual report on Form 10-K for the year ended December 31, 2023 as well as Xencor's subsequent filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended to date. All forward-looking statements are qualified in their entirety by this cautionary statement and Xencor undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof, except as required by law.

View source version on businesswire.com: https://www.businesswire.com/news/home/20240909200873/en/

For Investors:

Charles Liles

cliles@xencor.com

(626) 737-8118

For Media:

Cassidy McClain

Inizio Evoke

cassidy.mcclain@inizioevoke.com

(619) 694-6291

Source: Xencor, Inc.

FAQ

When will Xencor (XNCR) start the Phase 1 study for XmAb942 in IBD?

Xencor plans to initiate the Phase 1 study for XmAb942 in inflammatory bowel diseases (IBD) in the fourth quarter of 2024, with interim data expected during the first half of 2025.

What are the clinical progress updates for Xencor's (XNCR) XmAb819 program?

XmAb819 has shown initial evidence of anti-tumor activity in recent dose-escalation cohorts, including RECIST responses. The company anticipates reaching target dose levels by year-end and plans to provide a clinical update around the initiation of the first dose expansion cohort during the first half of 2025.

When does Xencor (XNCR) plan to start clinical trials for plamotamab in autoimmune diseases?

Xencor plans to initiate a Phase 1b/2a proof-of-concept study for plamotamab in multi-drug resistant rheumatoid arthritis (MDR-RA) in the first half of 2025.

What is the timeline for Xencor's (XNCR) XmAb657 clinical development?

Xencor plans to initiate a first-in-human study for XmAb657, a CD19 x CD3 bispecific T-cell engager for autoimmune diseases, during the second half of 2025.