Affimed Shows Higher Exposure of AFM24 is Associated with Significantly Higher Response Rates and Progression-Free Survival in Refractory NSCLC Patients at AACR Annual Meeting

On April 29, 2025 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported findings on an exposure-outcome analysis of its innate cell engager (ICE) AFM24, in patients with advanced or metastatic non-small cell lung cancer (NSCLC) in a poster session at the 2025 Annual Meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Affimed, APR 29, 2025, View Source [SID1234652329]).

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The analysis is based on post-hoc exposure-response data from 72 NSCLC patients treated with 480 mg of AFM24 monotherapy or a combination of AFM24 with atezolizumab. For all patients, trough levels over time were used to calculate the patient’s mean exposure to AFM24. Patients were then split into high and low AFM24 exposure groups for the analysis using the respective median as a cut-off.

Key Findings from the Exposure-Response Analysis

Objective Response Rate (ORR): 33.3% in the high-exposure group vs. 5.6% in the low-exposure group (p=0.0059)
Disease Control Rate (DCR): 83.3% vs. 58.3% (p=0.0367)
Median Progression-Free Survival (mPFS): 7.33 vs. 2.86 months
Overall Survival (OS): Not yet mature in the high-exposure group vs. 13 months in the low-exposure group
A quartile analysis further confirmed the exposure-efficacy relationship, showing a stepwise increase in ORR from 0% in the lowest quartile to 50% in the highest. Subgroup analysis of 55 patients treated with AFM24 plus atezolizumab showed consistent results: 37.04% ORR in the high-exposure group vs. 7.14% in the low group. Importantly, higher exposure was not associated with an increased rate of more serious or severe adverse events.

"Advanced NSCLC is a devastating disease and remains an area of high unmet need," said Andreas Harstrick, MD, Chief Medical Officer of Affimed. "These findings strengthen our clinical rationale for dose optimization and highlight the potential of AFM24 – particularly in combination with atezolizumab – as a novel, chemotherapy-free, immunotherapy-based treatment approach. Importantly, the data suggest that achieving higher drug exposure early in treatment may prevent rapid disease progression."

Further Development

Pharmacokinetic (PK) modeling indicates that a 720 mg weekly dose of AFM24—previously established as safe—achieves target exposure levels by the second week of treatment that correspond to the high exposure group in the post-hoc analysis. Based on these findings, Affimed will include the 720 mg dose moving forward to optimize clinical benefit and reduce early progression risk.

"These data provide compelling evidence that higher exposure may translate to better outcomes in patients with advanced NSCLC," Dr. Harstrick added. "With dose optimization in hand, we are positioned to advance AFM24 in its potential to deliver durable benefit in a difficult-to-treat patient population."

Conclusions

The data show a strong correlation between exposure and clinical outcome with a significantly increased risk for early tumor progression in the low exposure group. PK modeling suggests that a dose of 720 mg AFM24 weekly will result in exposure levels exceeding the cutoff for the high exposure group as early as week two. The 720 mg dose, which has already been established as safe in the phase 1 trial, will be used in future AFM24 studies.

More details about the programs for the AACR (Free AACR Whitepaper) Annual Meeting 2025 are available online at AACR (Free AACR Whitepaper) Annual Meeting 2025 | Meetings | AACR (Free AACR Whitepaper).

About AFM24
AFM24 is a tetravalent, bispecific ICE that activates the innate immune system by binding to CD16A on innate immune cells and epidermal growth factor receptors (EGFR), a protein widely expressed on solid tumors, to kill cancer cells. Generated by Affimed’s fit-for-purpose ROCK platform, AFM24 represents a distinctive mechanism of action that uses EGFR as a docking site to engage innate immune cells for tumor cell killing through antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

Sandoz enters global collaboration license agreement with Henlius to commercialize leading oncology therapy, ipilimumab, in multiple indications

On April 29, 2025 Sandoz (SIX:SDZ/OTCQX:SDZNY), the global leader in generic and biosimilar medicines, reported that it has signed a global collaboration agreement with Shanghai Henlius Biotech, Inc. (Henlius, HKEX:02696) to commercialize a biosimilar of leading oncology therapy, ipilimumab (Press release, Shanghai Henlius Biotech, APR 29, 2025, View Source [SID1234652328]). The agreement is milestone-based for a total consideration of up to USD 301 million, including an upfront payment of USD 31 million, and will target net reference-medicine sales of USD 2.5 billion[1].

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Under the terms of the agreement, Sandoz has exclusive commercial rights for a biosimilar of ipilimumab in Australia, Canada, Europe, Japan and the US. The core sequence patent for ipilimumab expired in March 2025 in the US and will expire no later than February 2026 in the EU.

Richard Saynor, CEO of Sandoz, said: "The global burden of cancer continues to grow and the potential to address unmet patient needs has never been greater.[3] This agreement offers us the chance to reach many more millions of patients, while helping to drive the long-term sustainability of healthcare systems."

The reference medicine, ipilimumab, is a monoclonal (CTLA-4) antibody-blocking medication, which is used alone or with other medicines to treat certain types of colorectal cancer, esophageal cancer, hepatocellular carcinoma (a type of liver cancer), malignant pleural mesothelioma, melanoma, non-small cell lung cancer, and renal cell carcinoma (a type of kidney cancer).[4,5,6]

Henlius is developing its own proposed biosimilar of ipilimumab in an integrated Phase I/III trial in the unresectable hepatocellular carcinoma setting, targeting 656 patients to be enrolled (NCT06841185).

Sandoz is developing its own proposed biosimilar of nivolumab in an integrated Phase I/III trial in the advanced melanoma setting, targeting 720 patients to be enrolled (NCT06587451). The reference medicine, nivolumab, (Opdivo**) is a monoclonal (PD-1) antibody-blocking medication, which is used alone or with other medicines to treat more than 10 different cancer types. In combination with ipilimumab, nivolumab is indicated for the treatment of melanoma, malignant pleural mesothelioma, renal cell carcinoma, certain types of colorectal cancer, esophageal cancer, non-small cell lung cancer and hepatocellular carcinoma.[7,8]

Sandoz is the leading biosimilar provider globally and has recently moved up to third position in the US, with a strategic ambition to occupy the leading position in that market.[9] The Company’s industry-leading biosimilars pipeline comprises 28 molecules, complemented by around 450 generic pipeline medicines to support its goal of sustainable and broadly-based long-term growth. The marketed biosimilar oncology portfolio includes Rixathon, Zarzio, Ziextenzo, and Binocrit. This year, Sandoz expects to launch its biosimilars Wyost/Jubbonti (denosumab) in the US in the second quarter and in Europe in the fourth quarter.

VerImmune Awarded ~$470K CDMRP Grant to Drive Innovation in ViP-Based Therapeutics for Advanced Melanoma

On April 29, 2025 VerImmune, Inc. ("VerImmune"), a biotechnology company developing innovative Virus-inspired Particle (ViP) modalities, reported it has been awarded a ~$470,000 USD research grant (MRP Idea Award) from the U.S. Department of Defense (DoD) Melanoma Research Program (MRP), managed by the office of Congressionally Directed Medical Research Programs (CDMRP) (Press release, VerImmune, APR 29, 2025, View Source [SID1234652326]).

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The award will support the development of novel candidates based on VerImmune’s ViP technology for the treatment of advanced or rare melanoma cancers.

The MRP received 136 compliant applications and recommended funding for only nine, placing VerImmune’s application in the top 6.6% of submissions.

"Receiving this award from such a highly competitive pool clearly demonstrates the innovation and groundbreaking work we are doing at VerImmune to develop therapies for patients with unmet medical needs," said Joshua Wang, Founder and CEO of VerImmune, Inc. "We are committed to advancing our ViP platform to address critical healthcare challenges and look forward to utilizing this funding to drive our efforts in melanoma and other cancers."

Tonix Pharmaceuticals Presented Preclinical Data on Gastric Cancer Models at the American Association for Cancer Research (AACR) 2025 Annual Meeting

On April 29, 2025 Tonix Pharmaceuticals Holding Corp. (Nasdaq: TNXP) (Tonix or the Company), a fully-integrated biopharmaceutical company with marketed products and a pipeline of development candidates, reported data in a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2025 Annual Meeting, held April 25-30, 2025, in Chicago, IL (Press release, TONIX Pharmaceuticals, APR 29, 2025, View Source [SID1234652325]). A copy of the Company’s presentation is available under the Scientific Presentations tab of the Tonix website at www.tonixpharma.com. The presentation titled, "TFF2-mediated CXCR4 partial agonism outperforms CXCR4 antagonism in reducing murine gastric cancer by suppressing PMN-MDSC generation," demonstrated positive data in gastric cancer animal models. In the AACR (Free AACR Whitepaper) presentation, a fusion protein of murine trefoil factor family member 2- murine serum albumin (mTFF2-MSA) was studied. Tonix is developing human TFF2-human serum albumin (hTFF2-HAS) as TNX-1700.

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"The combination therapy of mTFF2-MSA with anti-PD1 treatment shows promise in reducing immunosuppression in the tumor microenvironment (TME) in animal models," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals. "We are excited to develop TNX-1700 (TFF2-HAS) as the lead program in our immuno-oncology pipeline, by testing potential dosing strategies, and establishing potential clinical biomarkers through preclinical models."

Immunosuppressive neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are a major component in solid tumors that significantly hinder anti-tumor activity1,2. Despite being short-lived, their continuous replenishment from the bone marrow sustains their potent immunosuppression in the TME3. Stromal cells in the TME promote immunosuppression by recruiting MDSCs via secretion of CXCL12. Trefoil Factor 2 (TFF2), a secreted peptide of the trefoil factor family, has displayed activity as a partial agonist of CXCR44,5. Data presented in the poster demonstrated that TFF2-MSA selectively reduces immunosuppressive neutrophils and cancer-driven granulopoiesis. Treatment with TFF2-MSA, in combination with an anti-PD1 antibody, induced robust anti-tumoral CD8+ T cell responses, inhibiting tumor invasion. TFF2 reduction correlated with elevated PMN-MDSCs in gastric cancer patients, highlighting the potential negative correlation between TFF2 and PMN-MDSCs levels.

About Trefoil Factor Family Member 2 (TFF2)

Human TFF2 is a secreted protein, encoded by the TFF2 gene in humans, that is expressed in gastrointestinal mucosa where it functions to protect and repair mucosa. TFF2 is also expressed at low levels in splenic immune cells and is now appreciated to have intravascular roles in the spleen and in the tumor microenvironment. In gastric cancer, TFF2 is epigenetically silenced, and TFF2 is suggested to be protective against cancer development through several mechanisms. Tonix is developing TNX-1700 (rTFF2-HSA) for the treatment of gastric and colon cancers under a license from Columbia University. The inventor of the core technology at Columbia is Dr. Timothy Wang, who is an expert in the molecular mechanisms of carcinogenesis whose research has focused on the carcinogenic role of inflammation in modulating stem cell functions. Dr. Wang demonstrated that knocking out the mTFF2 gene in mice leads to faster tumor growth and that overexpression of TFF2 markedly suppresses tumor growth by curtailing the homing, differentiation, and expansion of MDSCs to allow activation of cancer-killing CD8+ T cells. He went on to show that a novel engineered form of recombinant murine TFF2 (mTFF2-CTP) had an extended half-life in vivo and was able to suppress MDSCs and tumor growth in an animal model of colorectal cancer. Later, he showed in gastric cancer models that suppressing MDSCs using chemotherapy enhances the effectiveness of anti-PD1 therapy and significantly reduces tumor growth. Dr. Wang proposed the concept of employing rTFF2 in combination with other therapies in cancer prevention and early treatment.

Regeneron Reports First Quarter 2025 Financial and Operating Results

On April 29, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the first quarter of 2025 and provided a business update (Press release, Regeneron, APR 29, 2025, View Source [SID1234652324]).

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"Regeneron has one of the most exciting pipelines in the industry, with unmatched diversity, scientific distinction, and potential to help millions of patients," said Leonard S. Schleifer, M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron. "We are laser focused on fulfilling the promise of this pipeline by advancing our clinical programs, and expect several important data readouts this year. We are also working to ensure our four blockbuster medicines reach even more patients who could benefit, with year-to-date progress including regulatory approvals for Dupixent in CSU in the U.S. and COPD in Japan."

Financial Highlights

($ in millions, except per share data) Q1 2025 Q1 2024 % Change
Total revenues $ 3,029 $ 3,145 (4 %)
GAAP net income $ 809 $ 722 12 %
GAAP net income per share – diluted $ 7.27 $ 6.27 16 %
Non-GAAP net income(a) $ 928 $ 1,116 (17 %)
Non-GAAP net income per share – diluted(a) $ 8.22 $ 9.55 (14 %)

"We have made meaningful progress across our pipeline so far in 2025, including four regulatory approvals, nine regulatory submissions, and are poised to report pivotal or proof-of-concept data across programs in immunology, oncology, hematology, internal medicine, and rare diseases later this year," said Christopher Fenimore, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "We continue to deploy capital with the goal of maximizing long-term shareholder value, with a focus on internal investment in our research, development, and commercial capabilities, along with returning capital directly to our shareholders through opportunistic share repurchases and our dividend program, which we initiated earlier this year."

Business Highlights

Key Pipeline Progress
Regeneron has approximately 45 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

Dupixent (dupilumab)

In April 2025, the U.S. Food and Drug Administration (FDA) approved Dupixent for the treatment of adults and adolescents aged 12 years and older with CSU who remain symptomatic despite antihistamine treatment.
In March 2025, Japan’s Ministry of Health, Labour and Welfare (MHLW) approved Dupixent for the treatment of patients with COPD.
The Company and Sanofi presented positive results from the pivotal Phase 2/3 trial in adults with moderate-to-severe bullous pemphigoid at the 2025 American Academy of Dermatology (AAD) Annual Meeting. In February 2025, the FDA accepted for priority review the supplemental Biologics License Application (sBLA) for Dupixent in bullous pemphigoid, with a target action date of June 20, 2025. A regulatory application has also been submitted in the European Union (EU).

EYLEA HD (aflibercept) 8 mg

In April 2025, the FDA accepted for priority review an sBLA for both the treatment of macular edema following RVO, and broadening the dosing schedule to include every 4-week (monthly) dosing across approved indications. The FDA target action date is August 19, 2025, following the use of a priority review voucher.
The FDA issued a Complete Response Letter (CRL) for the EYLEA HD pre-filled syringe on April 23, 2025. The Company held several teleconferences with the FDA to better understand the contents of the CRL, and believes the key outstanding issue relates to a question posed by the FDA to a third-party component supplier. This component supplier has expeditiously responded to FDA requests for information. The CRL did not identify any issues with the safety or efficacy of EYLEA HD, the usability of the device, proposed labelling, or pre-approval inspection findings.
In April 2025, the FDA issued a CRL regarding the sBLA for the addition of extended dosing intervals. The FDA indicated that the submitted data did not support extended dosing intervals greater than every 16 weeks. The Company is evaluating the FDA’s decision.
The Company presented positive results from the Phase 3 QUASAR trial for the treatment of patients with macular edema following RVO, including those with central, branch, and hemiretinal vein occlusions, at the Angiogenesis, Exudation, and Degeneration (Angiogenesis) 2025 annual meeting.
The Company announced positive three-year (156-week) results from an extension study of the Phase 3 PULSAR trial in patients with wet age-related macular degeneration (wAMD). Similar to the three-year results for the pivotal PHOTON trial in diabetic macular edema (DME), the longer-term wAMD data demonstrated the vast majority of patients who entered the extension study sustained the visual gains and anatomic improvements achieved by the end of the second year, while also achieving substantially longer treatment intervals. The results were presented at the Angiogenesis 2025 annual meeting.

Oncology Programs

The Company submitted an sBLA to the FDA and a regulatory application in the EU for Libtayo (cemiplimab) in adjuvant CSCC based upon data from a Phase 3 trial which demonstrated that adjuvant treatment with Libtayo was the first and only immunotherapy that led to a statistically significant and clinically meaningful improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk CSCC after surgery.
The FDA accepted for review the resubmission of the BLA for odronextamab, a bispecific antibody targeting CD20 and CD3, in relapsed/refractory (R/R) follicular lymphoma, with a target action date of July 30, 2025.
The FDA accepted for review the resubmission of the BLA for linvoseltamab, a bispecific antibody targeting BCMA and CD3, in R/R multiple myeloma, with a target action date of July 10, 2025.
The European Commission (EC) granted conditional marketing approval of Lynozyfic (linvoseltamab) to treat adults with R/R multiple myeloma. The indication is specific to those who have received at least three prior therapies including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, and have demonstrated disease progression on the last therapy.
Enrollment was completed in a Phase 3 confirmatory trial (LINKER-MM3) for linvoseltamab in R/R multiple myeloma.

Other Programs

The Company presented updated data from the Phase 1/2 trial of DB-OTO, an AAV-based gene therapy, in children with profound genetic hearing loss due to variants of the otoferlin (OTOF) gene at the Association for Research in Otolaryngology’s (ARO) 48th Annual MidWinter Meeting. The data showed that 11 out of 12 children treated demonstrated a notable response, with improved hearing at various decibel hearing levels. This included updated results from the first child dosed, who received treatment at 10 months of age and at 48 weeks post-treatment showed continued near-normal levels of hearing, as well as formal speech perception improvements between 48- and 72-weeks post-treatment.
A Phase 3 study for itepekimab, an antibody to IL-33, in chronic rhinosinusitis with nasal polyposis (CRSwNP) was initiated.
A Phase 2 study for REGN5381, an agonist antibody to NPR1, in uncontrolled hypertension was initiated.
A Phase 2 study for REGN7544, an antagonist antibody to NPR1, in sepsis-induced hypotension was initiated.
The FDA granted Orphan Drug designation for mibavademab, an agonist antibody to leptin receptor (LEPR), in generalized lipodystrophy; a Phase 3 study is ongoing.

Corporate Updates

The Company reached resolution of its patent infringement litigation related to Biocon’s EYLEA (aflibercept) Injection 2 mg biosimilar product. The settlement precludes Biocon from launching its biosimilar product in the United States until the second half of 2026. All intellectual property-related litigation with Biocon in the United States has been dismissed.
The Company announced a 10-year agreement with FUJIFILM Diosynth Biotechnologies (Fujifilm) to manufacture and supply Regeneron’s commercial bulk drug product at Fujifilm’s North Carolina campus. The agreement is anticipated to nearly double the Company’s large-scale manufacturing capacity in the United States.
First Quarter 2025 Financial Results

Revenues

($ in millions) Q1 2025 Q1 2024 % Change
Net product sales:
EYLEA HD – U.S. $ 307 $ 200 54 %
EYLEA – U.S. 736 1,202 (39 %)
Total EYLEA HD and EYLEA – U.S. 1,043 1,402 (26 %)
Libtayo – U.S. 192 159 21 %
Libtayo – ROW** 93 105 (11 %)
Total Libtayo – Global 285 264 8 %
Praluent – U.S. 57 70 (19 %)
Evkeeza – U.S. 31 24 29 %
Inmazeb – ROW — 1 (100 %)
Total net product sales 1,416 1,761 (20 %)

Collaboration revenue:
Sanofi 1,183 910 30 %
Bayer 344 356 (3 %)
Other 4 1 *
Other revenue 82 117 (30 %)
Total revenues $ 3,029 $ 3,145 (4 %)

* Percentage not meaningful
** Rest of world (ROW)

Net product sales of EYLEA HD increased in the first quarter of 2025, compared to the first quarter of 2024, primarily due to higher sales volumes.

Net product sales of EYLEA in the first quarter of 2025, compared to the first quarter of 2024, were negatively impacted by (i) lower volume as a result of continued competitive pressures (as described below), loss in market share to compounded bevacizumab due to patient affordability constraints, and the continued transition of patients to EYLEA HD, and (ii) a lower net selling price.

In addition, total EYLEA and EYLEA HD net product sales were negatively impacted by lower wholesaler inventory levels at the end of the first quarter of 2025 compared to the end of the fourth quarter of 2024. Total EYLEA and EYLEA HD net product sales decreased 30% on a sequential basis; however, physician unit demand decreased sequentially by 11%.

EYLEA net product sales have been, and are likely to continue to be, negatively impacted by increased competition from other anti-VEGF products, including biosimilars, as well as the transition of patients from EYLEA to EYLEA HD. In addition, if independent not-for-profit patient assistance funds that provide copay assistance are unable to support eligible patients, this will likely have a continued negative impact on patient affordability resulting in lower utilization of higher-cost anti-VEGF agents.

Sanofi collaboration revenue increased in the first quarter of 2025, compared to the first quarter of 2024, due to an increase in the Company’s share of profits from the commercialization of antibodies, which were $1.018 billion and $804 million in the first quarter of 2025 and 2024, respectively. The change in the Company’s share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales.

Refer to Table 4 for a summary of collaboration revenue.

Operating Expenses

GAAP %
Change
Non-GAAP(a) %
Change

($ in millions) Q1 2025 Q1 2024 Q1 2025 Q1 2024
Research and development (R&D) $ 1,327 $ 1,248 6 % $ 1,186 $ 1,122 6 %
Acquired in-process research and development (IPR&D) $ 12 $ 7 71 % * * n/a
Selling, general, and administrative (SG&A) $ 633 $ 689 (8 %) $ 537 $ 584 (8 %)
Cost of goods sold (COGS) $ 266 $ 240 11 % $ 217 $ 196 11 %
Gross margin on net product sales(c) 81% 86% 85% 89%
Cost of collaboration and contract manufacturing (COCM) $ 199 $ 193 3 % * * n/a
Other operating expense (income), net $ — $ 15 (100 %) * $ — — %

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded

GAAP and non-GAAP R&D expenses increased in the first quarter of 2025, compared to the first quarter of 2024, driven by the advancement of the Company’s clinical pipeline and higher personnel-related costs.
GAAP and non-GAAP gross margin on net product sales was adversely impacted by higher inventory write-offs and reserves in the first quarter of 2025 compared to the first quarter of 2024.
Other Financial Information

GAAP other income (expense), net included the recognition of net unrealized gains on equity securities of $140 million in the first quarter of 2025, compared to $196 million of net unrealized losses in the first quarter of 2024.

In the first quarter of 2025, the Company’s GAAP effective tax rate (ETR) was 10.6%, compared to (3.0%) in the first quarter of 2024. The GAAP ETR increased in the first quarter of 2025, compared to the first quarter of 2024, due to lower tax benefits from less stock option exercises. In the first quarter of 2025, the non-GAAP ETR was 11.6%, compared to 6.1% in the first quarter of 2024.

A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

Capital Allocation

In February 2025, the Company’s board of directors authorized a new share repurchase program to repurchase up to an additional $3.0 billion of the Company’s common stock. During the first quarter of 2025, the Company repurchased shares of its common stock and recorded the cost of the shares, or $1.052 billion, as Treasury Stock. As of March 31, 2025, an aggregate of $3.874 billion remained available for share repurchases under the Company’s share repurchase programs.

In April 2025, the Company’s board of directors declared a cash dividend of $0.88 per share on the Company’s common stock and Class A stock, payable on June 6, 2025 to shareholders of record as of May 20, 2025.