On May 6, 2025 CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on anti-cancer therapies, reported that poster presentations of preclinical data of CS2011 (EGFR/HER3 bispecific antibody), CS5007 (EGFR/HER3 bispecific ADC), CS5005 (SSTR2 ADC) and CS5006 (ITGB4 ADC), key assets in CStone Pipeline 2.0, have been delivered at the 2025 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, CStone Pharmaceauticals, MAY 6, 2025, View Source [SID1234652605]).

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Key Highlights:

CS2011 (EGFR/HER3 bispecific antibody):
EGFR and HER3 are members of the human epidermal growth factor receptor (HER) family and are validated therapeutic targets in advanced solid tumors. EGFR overexpression drives tumor progression in approximately 70% of colorectal cancers (CRC), 60% of lung cancers, and over 90% of head and neck squamous cell carcinomas (HNSCC). Meanwhile, HER3 upregulation frequently emerges as a resistance mechanism to MAPK/PI3K inhibitors, EGFR tyrosine kinase inhibitors (TKIs), and hormone therapies. CS2011 is a bispecific antibody with high binding affinity to both EGFR and HER3. It effectively blocks downstream signaling of both targets, thereby inhibiting tumor growth on EGFR/HER3 positive tumor cells.

1. CS2011 targets almost all HER family signaling except HER2 homodimers, addressing tumor heterogeneity effectively.

2. CS2011 demonstrates potent binding affinity to EGFR and/or HER3 individually and enhanced dual binding affinity to EGFR and HER3 concurrently driven by avidity-based synergy.

3. CS2011 inhibits tumor growth by binding to EGFR and/or HER3-positive tumor cells.

4. CS2011 shows superior in vivo and in vitro anti-tumor activity versus potential major competitors.

（1） Compared to anti-EGFR, anti-HER3 and competing bispecific antibody, CS2011 induces faster and deeper internalization in tumor cells across varying EGFR & HER3 expression levels.

（2） CS2011 demonstrated potent inhibition of EGFR downstream signaling, comparable to anti-EGFR antibodies, and superior inhibition of HER3-mediated signaling compared to competitive bispecific antibody.

（3） CS2011 exhibited robust anti-proliferative activity in tumor cells with diverse EGFR and HER3 expression levels.

（4） In in vivo CDX tumor models, CS2011 demonstrated superior tumor-growth inhibition compared to anti-EGFR or anti-HER3 monoclonal antibodies alone and showed comparable efficacy to the combination treatment.

5. CS2011 exhibited a pharmacokinetic (PK) profile comparable to those of monoclonal antibodies in rodents.

In summary, CS2011 has demonstrated potent blockage activity on EGFR and HER3 and exhibited synergistic effects on their downstream signaling. It thereby shows the potent tumor growth inhibitory effects in in vitro and in vivo experiments. The patent of CS2011 has been filed in March 2025, and its Investigational New Drug (IND) application is expected to be submitted in the near term.

CS5007 (EGFR/HER3 bispecific ADC):
CS5007 is a bispecific ADC targeting both EGFR and HER3, developed with CStone’s proprietary ADC platform. It is composed of EGFR/HER3 bispecific antibody backbone (CS2011), a hydrophilic β-glucuronide linker and a clinically validated topoisomerase I inhibitor, Exatecan. This integrated approach, featuring precise targeting, optimized linker stability, and proven therapeutic payload, positions CS5007 as a potential best-in-class candidate for precision oncology.

1. CS5007 targets almost all human epidermal growth factor receptor (HER) family signaling except for HER2 homodimers, covering broad tumor types and effectively addressing tumor heterogeneity.

2. CS5007 demonstrated high-affinity binding to EGFR single-positive, HER3 single-positive, and EGFR/HER3 double-positive tumor cells.

3. CS5007 triggered high-rate internalization on tumor cells.

4. CS5007 demonstrated potent, antigen-dependent cytotoxicity against tumor cells in vitro across varying EGFR and HER3 expression levels and showed robust tumor-growth inhibition in CDX models.

5. CS5007 exhibited superior in vitro stability compared to ADCs conjugated with tetrapeptide and dipeptide linkers. After 7 days of incubation in human/monkey serum, it retained approximately 70% of its drug payload, indicating a minimal release rate.

6. CS5007 exhibited comparable pharmacokinetic (PK) profile to those ADCs composed of monoclonal antibodies in rodents.

CS5007 demonstrates strong affinity for EGFR- and/or HER3-positive tumor cells and induces efficient internalization. Preclinical studies have shown excellent antitumor activity, favorable safety, and pharmacokinetic profiles. The patent of CS5007 has been filed in March 2025. Preclinical findings support further IND-enabling studies and clinical investigations in various advanced solid tumors.

CS5005 (SSTR2 ADC):
Somatostatin receptor 2 (SSTR2) is a G protein-coupled receptor (GPCR) that is overexpressed in various solid tumors, including neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and small cell lung cancer (SCLC). Due to its tumor-selective expression profile, SSTR2 has emerged as a promising target in the field of precision oncology.

CS5005 is a first-in-class, SSTR2-targeting ADC, composed of CStone’s proprietary anti-SSTR2 antibody with high affinity and selectivity, hydrophilic β-glucuronide linker, and potent topoisomerase I inhibitor, Exatecan. In preclinical studies, CS5005 demonstrated potent, antigen-dependent tumor growth inhibition that was not affected by co-administration with SSA-derived therapies. Additionally, CS5005 exhibited superior stability, monoclonal antibody-like pharmacokinetic (PK) properties, and favorable tolerability in preliminary non-human primate toxicity studies.

1. CS5005 demonstrated high affinity to SSTR2-positive cell lines and induced high-rate internalization on tumor cells.

2. CS5005 exhibited cross-reactivity with SSTR2-expressing cells in non-human primates and demonstrated selective binding to SSTR2 with minimal interaction with other SSTRs.

3. CS5005 demonstrated potent antigen-dependent cytotoxic activity against tumor cells in vitro and robust tumor-growth inhibition in CDX tumor model.

4. The antitumor activity of CS5005 (SSTR2-DXd) is not compromised by concomitant ligand-derived treatments (e.g., octreotide, Lutathera), thereby avoiding drug-drug interference commonly observed with current anti-SSTR2 therapies.

5. CS5005 demonstrated superior in vitro stability due to its proprietary linker, outperforming ADCs conjugated with well-validated dipeptide and tetrapeptide linkers.

6. Superior pharmacokinetic (PK) properties of CS5005 in rodents.

7. Bioinformatics analysis of SCLC samples supports DLL3/SSTR2 dual targeting as a strategy to overcome tumor heterogeneity and expand the treatable patient population.

In summary, CS5005 is a first-in-class, SSTR2-targeting ADC designed to selectively eliminate SSTR2-positive tumors, including small cell lung cancer, neuroendocrine carcinoma, and neuroendocrine tumors. It is composed of CStone’s proprietary high-affinity, high-selectivity anti-SSTR2 antibody, CStone’s proprietary hydrophilic β-glucuronide linker, and potent TOP1 inhibitor payload. CS5005 has demonstrated robust antitumor activity in both in vitro and in vivo studies, supporting its progression toward IND submission and clinical development. The patent of de novo antibody backbone of CS5005 has been filed in the first half of 2024. CS5008, an SSTR2/DLL3 bispecific ADC is under development. By simultaneously targeting SSTR2 and DLL3 that frequently co-express in SCLC, NETs, NECs and others, CS5008 aims to overcome tumor heterogeneity, a challenge faced by mono-specific therapies.

CS5006 (ITGB4 ADC):
CS5006 is a first-in-class antibody-drug conjugate (ADC) targeting the novel antigen integrin β4 (ITGB4), developed using CStone’s proprietary ADC platform. Leveraging an internally developed machine learning-based bioinformatics algorithm alongside rigorous in-house experimental validation, CStone identified elevated ITGB4 expression across multiple tumor types—including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), and head and neck squamous cell carcinoma (HNSCC)—with minimal expression observed in normal tissues. Preclinical in vivo and in vitro studies have demonstrated CS5006’s promising therapeutic potential, highlighting its ability to effectively killing tumor cells.

1. Bioinformatics analysis identified high ITGB4 expression in colorectal tumor tissues, supporting ITGB4 as a promising tumor-associated antigen for CRC. In the tumor microenvironment, ITGB4 was selectively overexpressed on tumor cells while remaining low expression in normal tissues.

2. Immunohistochemistry (IHC) staining confirmed limited ITGB4 expression in normal tissue but high expression in tumor tissues from patients with CRC, sq-NSCLC, HNSCC and ESCC.

3. ITGB4 antibody demonstrated high affinity and internalization rate.

4. CS5006 preclinical proof-of-concept models using ITGB4-vedotin and ITGB4-DXd showed potent antitumor activity in both in vitro and in vivo studies, along with favorable pharmacokinetic (PK) profiles.

（1） ITGB4-vedotin exhibited strong antigen-dependent cytotoxicity in ITGB4-positive tumor cell lines in vitro and demonstrated potent antigen-dependent tumor inhibition in CDX models in vivo.

（2） ITGB4-DXd also exhibited potent antigen-dependent cytotoxicity in vitro and strong tumor-inhibitory effects in vivo CDX tumor models.

（3） Both ITGB4-vedotin and ITGB4-DXd exhibited favorable PK characteristics.

In summary, CS5006 is a first-in-class ADC targeting the novel tumor antigen ITGB4 and is currently undergoing comprehensive preclinical evaluation. Preclinical data have demonstrated strong antitumor activity across multiple animal models, particularly in solid tumors such as non-small cell lung cancer, head and neck squamous cell carcinoma, and esophageal squamous cell carcinoma. The compound also exhibited good tolerability, providing strong support for its further clinical development. The patent of CS5006 has been filed in April 2023.

Poster Information:

Poster Title

Poster Number

CS2011: A novel bispecific antibody targeting EGFR and HER3 that
demonstrates promising anti-tumor activity in preclinical evaluation

2927

CS5007: A novel EGFR and HER3 dual-targeted antibody-drug
conjugate (ADC) with potent antitumor activity in preclinical studies

2954

CS5005: A novel SSTR2-targeted antibody-drug conjugate (ADC) with
robust anti-tumor activity in preclinical studies

4751

CS5006: A novel integrin β4-targeted antibody-drug conjugate (ADC)
with robust antitumor activity in preclinical studies

2953

On May 6, 2025 Astrazeneca and Daiichi Sankyo reported positive high-level results from the DESTINY-Breast11 Phase III trial showed Enhertu (trastuzumab deruxtecan) followed by paclitaxel, trastuzumab and pertuzumab (THP) demonstrated a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) rate versus standard of care (dose-dense doxorubicin and cyclophosphamide followed by THP [ddAC-THP]) when used in the neoadjuvant setting (before surgery) in patients with high-risk, locally advanced HER2-positive early-stage breast cancer (Press release, AstraZeneca, MAY 6, 2025, View Source [SID1234652604]). Pathologic complete response is defined as no evidence of invasive cancer cells in the removed breast tissue and lymph nodes following treatment.

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The secondary endpoint of event-free survival (EFS) was not mature at the time of analysis; however, EFS data showed an early positive trend favouring Enhertu followed by THP compared to standard of care. The trial will continue to follow EFS.

Approximately one in three patients with early-stage breast cancer are considered high risk, as they are more likely to experience disease recurrence and have a poor prognosis.1,2 Achieving pCR in early-stage HER2-positive breast cancer is associated with improved long-term outcomes.2,3 The current standard of care in many regions of the world in this neoadjuvant setting involves combination chemotherapy regimens.2 These regimens often include anthracyclines, which can be challenging for patients to tolerate and may result in long-term cardiovascular side effects.4 Further, nearly half of patients who receive neoadjuvant treatment do not achieve pCR, reinforcing the need for new treatment options.2,3

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "The clinically meaningful improvement in pathologic complete response and the safety data seen in DESTINY-Breast11 highlight the potential of Enhertu to challenge the current standard of care in early-stage HER2-positive breast cancer. Enhertu is already an important treatment option in the metastatic setting, and these data have the potential to allow this medicine to move into early stages of disease where cure is possible."

Ken Takeshita, Global Head, R&D, Daiichi Sankyo, said: "There are still many patients with early-stage breast cancer who do not achieve a pathologic complete response with treatment in the neoadjuvant setting, increasing the risk of disease recurrence. These topline results from DESTINY-Breast11 demonstrate that Enhertu followed by THP could offer patients with HER2-positive breast cancer a promising new treatment approach prior to surgery, setting more patients on a path towards a potential cure."

Enhertu followed by THP showed an improved safety profile compared to ddAC-THP. The safety profiles of Enhertu and THP were consistent with the known profiles of each individual medicine with no new safety concerns identified. Rates of interstitial lung disease were similar across the Enhertu followed by THP and the ddAC-THP arms as determined by an independent adjudication committee.

Following a recommendation by the Independent Data Monitoring Committee, patient enrolment in a third arm of the trial evaluating Enhertu alone was closed after a previous interim efficacy assessment of the trial arms.

Data from DESTINY-Breast11 will be presented at an upcoming medical meeting and shared with regulatory authorities.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Enhertu has demonstrated improved outcomes in six Phase III breast cancer trials across different subtypes and stages of disease, including the recently announced DESTINY-Breast09 Phase III trial in the 1st-line HER2-positive metastatic setting. Enhertu is also being studied in several ongoing breast cancer trials including the DESTINY-Breast05 Phase III trial which is evaluating Enhertu in the high-risk adjuvant early HER2-positive setting.

Notes

HER2-positive early breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide.5 More than two million breast cancer cases were diagnosed in 2022, with more than 665,000 deaths globally.5

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast cancer.6 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.7 Approximately one in five cases of breast cancer are considered HER2-positive.8

DESTINY-Breast11
DESTINY-Breast11 is a global, multicentre, randomised, open-label, Phase III trial evaluating the efficacy and safety of neoadjuvant Enhertu (5.4mg/kg) monotherapy or Enhertu followed by THP vs. the standard of care regimen in patients with high-risk (lymph node positive [N1-3] or primary tumour stage T3-4), locally advanced or inflammatory HER2-positive early-stage breast cancer.

Patients were randomised 1:1:1 to receive either eight cycles of Enhertu monotherapy; four cycles of Enhertu followed by four cycles of THP; or four cycles of ddAC (dose-dense doxorubicin and cyclophosphamide) followed by four cycles of THP.

The primary endpoint of DESTINY-Breast11 is pCR (absence of invasive disease in the breast and lymph nodes). Secondary endpoints include EFS, invasive disease-free survival, overall survival and safety.

DESTINY-Breast11 enrolled 927 patients across multiple sites in Asia, Europe, North America and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more) prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally approved test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4mg/kg) is approved in more than 50 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication is contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population.

Enhertu (5.4mg/kg) is approved in the US and other countries for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on the results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US is contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as monotherapy or in combination or sequentially with other anti-cancer therapies across multiple HER2-targetable cancers.

On May 6, 2025 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) (Actinium or the Company), a pioneer in the development of targeted radiotherapies, reported that the first patient was enrolled on the trial studying Iomab-ACT targeted conditioning with a commercial CAR-T therapy at the University of Texas Southwestern Medical Center (UTSW) (NCT06768905) (Press release, Actinium Pharmaceuticals, MAY 6, 2025, View Source [SID1234652603]). Initial clinical data from this trial is expected in the second half of 2025. Actinium is developing Iomab-ACT as a targeted radiotherapy conditioning agent intended to replace non-targeted chemotherapeutic conditioning agents such as Fludarabine and Cyclophosphamide (Flu/Cy) to address serious CAR-T related toxicities including immune effector cell-associated neurotoxicity (ICANS) and cytokine release syndrome (CRS), to potentially improve patient access and outcomes. Currently, there are seven CAR-T therapies approved for certain leukemias and lymphomas and multiple myeloma, that over 150,000 patients are diagnosed with annually. In 2024, the seven approved CAR-T therapies generated over $4 billion in sales and CAR-T therapies are forecasted to reach $12 billion in annual sales in 2030.

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Dr. Farrukh Awan, Professor of Medicine, Division of Hematology Oncology at UTSW said, "We are thrilled to initiate patient enrollment to study Iomab-ACT targeted radiotherapy conditioning with a commercial CAR-T therapy. Iomab-ACT is supported by compelling preclinical and clinical data, and we believe it has immense potential to eliminate the need for chemotherapy-based conditioning, which is a major barrier for many patients seeking CAR-T treatment. Despite the positive impact CAR-T therapy has had on patient outcomes, there is still significant room for improvement. We are optimistic that Iomab-ACT can transform CAR-T therapy conditioning if this trial demonstrates it has the ability to increase patients access and reduce the rates and severity of ICANS and CRS and also potentially improve patient outcomes. We are excited to begin treating patients with Iomab-ACT and eager to present our preliminary findings later this year."

Iomab-ACT targets CD45, a cell surface marker expressed on immune cells relevant to CAR-T therapy including lymphocytes and is the only clinical stage conditioning agent targeting CD45. Preclinical data demonstrated that Iomab-ACT can selectively target immune cells implicated in CAR-T toxicities, while sparing bone marrow stem cells, red blood cells and platelets. Preclinical and clinical data also showed that Iomab-ACT produces transient lymphodepletion that aligns with the CAR-T treatment process. This data supported the first clinical trial of Iomab-ACT with a novel CD19 CAR-T therapy in collaboration with Memorial Sloan Kettering Cancer Center (MSK) in patients heavily pretreated with relapsed and refractory B-cell Acute Lymphoblastic Leukemia (B-ALL) or Diffuse Large B-cell Lymphoma (DLBCL). In this study, no patients (0/4) developed ICANS of any grade, and minimal CRS. Iomab-ACT also demonstrated transient depletion of peripheral blood lymphocytes and monocytes, persistence of CAR T-cells up to 8 weeks and minimal non-hematologic toxicities. These positive findings supported the continued advancement of Iomab-ACT and the initiation of the commercial CAR-T trial at UTSW.

Sandesh Seth, Actinium’s Chairman and CEO, stated, "This is a pivotal moment for our Iomab-ACT CD45 targeted radiotherapy conditioning program. Iomab-ACT is a highly differentiated conditioning agent that has produced promising initial clinical results where multiple targeted conditioning approaches including monoclonal antibodies and antibody drug conjugates directed against a variety of targets have not achieved clinical success to date. Based on the promising initial outcomes from the pilot study of Iomab-ACT with a novel CD19 CAR-T, we are incredibly excited by the potential of this commercial CAR-T trial and future development path. With initial clinical data expected beginning in the second half of this year, we are making strong progress to achieving our goal of establishing Iomab-ACT as a universal targeted conditioning regimen for CAR-T and other cellular therapies."

Targeted Radiotherapy CAR-T Conditioning Opportunity

A multi-billion-dollar market opportunity exists for better conditioning in other areas of cellular therapy, such as CAR-T. Currently, there are seven CAR T-cell therapies targeting CD19 for lymphoma and leukemia and BCMA for multiple myeloma that are approved by the FDA with total sales of over $4.0 billion in 2024. The pipeline of CAR-T therapies in development has rapidly expanded, with the addressable patient population expected to nearly double and reach approximately 93,000 patients in the U.S. by 2030 based on the current pipeline of cellular therapies. The addressable market for Iomab-ACT is in line with the patient population for cellular therapies that is approximately150,000 patients annually across the indications in which CAR-T therapies are approved, as all patients receive conditioning of some type. We believe a potential blockbuster revenue opportunity exists for Iomab-ACT assuming it can provide clinical benefits related to adverse events related to CAR-T, longer duration of response or improved survival outcomes.

On May 6, 2025 Krystal Biotech, Inc. (the "Company") (NASDAQ: KRYS) reported financial results for the first quarter ending March 31, 2025 and provided a business update (Press release, Krystal Biotech, MAY 6, 2025, View Source [SID1234652602]).

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"We were thrilled to receive VYJUVEK approval in Europe, and with the potential expansion to Japan later in the year, we continue to make tremendous progress on our goal of delivering profound long-term benefit to DEB patients around the world," said Krish S. Krishnan, Chairman and CEO of Krystal Biotech. "With today’s announcement of our second clinical-stage ophthalmology program, the near-term initiation of our registrational study in DEB patients with eye lesions, and upcoming molecular readouts for our rare respiratory disease product candidates, KB407 and KB408, we are pushing forward a broad and expanded pipeline which we expect will ultimately demonstrate the power of HSV-1 based gene delivery in the lung, eye, and skin, and – most importantly – deliver meaningful benefit to patients."

VYJUVEK (beremagene geperpavec-svdt, or B-VEC)
for the Treatment of Dystrophic Epidermolysis Bullosa (DEB)

In April, the European Commission approved VYJUVEK for the treatment of wounds in patients with DEB who have mutations in the collagen type VII alpha 1 chain (COL7A1) gene, starting from birth. The Company is on track for its first European launch in Germany in mid-2025.
The Company recorded $88.2 million in VYJUVEK net product revenue for the first quarter of 2025. Gross margin for the quarter was 94%.
As of April, the Company has secured over 540 reimbursement approvals for VYJUVEK in the U.S. and continues to maintain strong access nationwide including positive access determinations for 97% of lives covered under commercial and Medicaid plans.
High patient compliance with weekly treatment while on drug continued at 83% as of the end of the quarter.
The Company continues to expect a decision by Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) on its Japan New Drug Application (JNDA) in 2H 2025.
In April, the British Journal of Dermatology published a case highlighting the success of VYJUVEK in promoting durable wound healing following surgical excision of a large squamous cell carcinoma (SCC) in a recessive DEB patient. The treated patient reported complete healing of their over 100 cm2 post-surgical wound after seven weeks of VYJUVEK therapy. Wound healing benefits were durable, with complete wound closure also observed upon clinical examination at four and ten month post-operative visits.
In April, the results of the Company’s open label extension (OLE) study of VYJUVEK in DEB patients were published in the American Journal of Clinical Dermatology.
Respiratory

KB407 for the treatment of cystic fibrosis (CF)

The Company continues to enroll Cohort 3 of CORAL-1, the Company’s multi-center, dose escalation study evaluating KB407 in patients with CF, regardless of their underlying genotype. The Company received full sanctioning of the study protocol by the Cystic Fibrosis Foundation Therapeutic Development Network in January and remains on track for an interim molecular data readout for Cohort 3 patients in mid-2025. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT05504837.
KB408 for the treatment of alpha-1 antitrypsin deficiency (AATD) lung disease

The Company continues to enroll in Cohort 2 and is working to enroll in Cohort 3 of SERPENTINE-1, the Company’s open label, single dose escalation study in adult patients with AATD with a Pi*ZZ or a Pi*ZNull genotype. Late last year, the Company announced successful SERPINA1 gene delivery and functional alpha-1 antitrypsin (AAT) expression reaching therapeutic levels as part of an interim clinical update for Cohorts 1 and 2 of SERPENTINE-1. Inhaled KB408 was safe and well-tolerated at both tested dose levels. The Company expects to report molecular results for the additional Cohort 2 and 3 patients later this year. Details about the study can be found at www.clinicaltrials.gov under NCT identifier: NCT06049082.
Ophthalmology

KB803 for the treatment of ocular complications of DEB

The Company continues to enroll in its ongoing natural history study to prospectively collect data on the frequency of corneal abrasions in patients with DEB and serve as a run-in period for patients who may be eligible to participate in the Company’s registrational Phase 3 study evaluating KB803’s effect on ocular complications of DEB. The Company expects to dose the first patient in the registrational KB803 Phase 3 IOLITE study later this month.
KB801 for the treatment of neurotrophic keratitis (NK)

In April, the U.S. Food and Drug Administration (FDA) cleared the Company’s investigational new drug (IND) application to evaluate KB801, the Company’s second clinical-stage ophthalmology program, for the treatment of NK. NK is a rare, degenerative corneal disease caused by nerve damage in the eye leading to corneal epithelial defects, ulcers, and perforation, with an estimated prevalence in the range of 10 to 50 cases per 100,000. KB801 was developed using the Company’s novel replication-defective, non-integrating HSV-1-based vector and is designed to deliver two transgene copies to the corneal epithelium as an eye drop to enable local nerve growth factor (NGF) production and corneal healing. Recombinant NGF eye drops have been shown to significantly improve corneal healing and are approved for the treatment of NK in multiple jurisdictions worldwide including the United States, but the short half-life of recombinant protein results in rapid clearance from the eye, thereby necessitating burdensome administration six times a day, and may lead to suboptimal treatment outcomes. Eye pain during treatment is also frequently reported.
In preclinical development, KB801 was shown to efficiently transduce corneal epithelial cells in vitro and in vivo leading to sustained NGF production in the front of the eye. By transducing the cells of the corneal epithelium to produce and secrete NGF, KB801 has the potential to significantly reduce the treatment burden for patients while also maintaining more consistent NGF levels in the front of the eye. Yesterday, the Company presented preclinical safety and efficacy data supporting the clinical development of KB801 at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting.
The Company expects to dose the first patient in EMERALD-1, the Company’s randomized, double-blind, placebo-controlled, multi-center Phase 1/2 study evaluating KB801 in moderate-to-severe NK patients, later this month.
Oncology

Inhaled KB707 for the treatment of solid tumors of the lung

Enrollment is ongoing in the Company’s KYANITE-1 study, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating inhaled KB707, as monotherapy or in combination, in patients with locally advanced or metastatic solid tumors of the lung. Near the end of last year, the Company announced early clinical evidence of monotherapy activity in heavily pre-treated patients with advanced non-small cell lung cancer (NSCLC) treated with inhaled KB707, achieving an objective response rate of 27% and disease control rate of 73% as of data cut-off. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT06228326.
A clinical update on the monotherapy cohort from KYANITE-1 is expected to be presented at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting next month.
Intratumoral KB707 for the treatment of injectable solid tumors

The Company continues to enroll in OPAL-1, a Phase 1/2 open label, multi-center, dose escalation and expansion study evaluating intratumoral KB707, either as monotherapy or in combination, in patients with locally advanced or metastatic solid tumor malignancies. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT05970497.
Aesthetics

KB301 for the treatment of dynamic wrinkles of the décolleté

Jeune Aesthetics is currently developing a décolleté-specific photo numeric scale for advanced clinical development of KB301. Jeune Aesthetics expects to align with the FDA on the scale and enroll the first subject in a multi-center, randomized, placebo-controlled Phase 2 study evaluating KB301 for the treatment of dynamic wrinkles of the décolleté in Q4 2025.
KB304 for the treatment of wrinkles

In February, Jeune Aesthetics completed enrollment in PEARL-2, an ongoing, randomized and placebo-controlled Phase 1 study evaluating KB304 for the treatment of wrinkles. Jeune Aesthetics expects to report top-line results from the study in 2H 2025. Details of the study can be found at www.clinicaltrials.gov under NCT identifier NCT06724900.
Dermatology

KB105 for the treatment of lamellar ichthyosis

The Company expects to initiate the Phase 2 portion of its KB105 Phase 1/2 JADE-1 trial evaluating KB105 for the treatment of TGM1-deficient lamellar ichthyosis in pediatric patients in 2026.
Pipeline expansion

The Company will be presenting preclinical data at the Society for Investigative Dermatology (SID) 2025 Annual Meeting later this week on early-stage dermatology genetic medicine candidates for the treatment of Hailey-Hailey and Darier diseases.
Financial Results for the Quarter Ended March 31, 2025:

Cash, cash equivalents, and investments totaled $765.3 million as of March 31, 2025.
Product revenue, net totaled $88.2 million and $45.3 million for the quarters ended March 31, 2025 and March 31, 2024, respectively.
Cost of goods sold totaled $5.0 million and $2.4 million for the quarters ended March 31, 2025 and March 31, 2024, respectively.
Research and development expenses for the quarter ended March 31, 2025 were $14.3 million, inclusive of $2.5 million of stock-based compensation, compared to $11.0 million, inclusive of stock-based compensation of $1.9 million for the quarter ended March 31, 2024.
Selling, general, and administrative expenses for the quarter ended March 31, 2025 were $32.7 million, inclusive of stock-based compensation of $11.0 million, compared to $26.1 million, inclusive of stock-based compensation of $7.4 million, for the quarter ended March 31, 2024.
Net income for the quarter ended March 31, 2025 was $35.7 million, or $1.24 per common share (basic) and $1.20 per common share (diluted). Net income for the quarter ended March 31, 2024 was $0.9 million, or $0.03 per common share (basic) and $0.03 per common share (diluted).
Financial Guidance

($ in millions) FY 2025 Guidance
Non-GAAP Research and Development ("R&D") and Selling, General and Administrative ("SG&A") expense(1) $150.0 – $175.0

(1) Refer to Non-GAAP Financial Measures section below for additional information. Non-GAAP combined R&D and SG&A expense guidance does not include stock-based compensation as we are currently unable to confidently estimate Full Year 2025 stock-based compensation expense. As such, we have not provided a reconciliation from forecasted non-GAAP to forecasted GAAP combined R&D and SG&A Expense in the above. This could materially affect the calculation of forward-looking GAAP combined R&D and SG&A Expense as it is inherently uncertain.

Conference Call

The Company will host an investor webcast on May 6, 2025, at 8:30 am ET.

Investors and the general public can access the live webcast at:
View Source

For those unable to listen to the live conference call, a replay will be available for 30 days on the Investors section of the Company’s website at www.krystalbio.com.

On May 6, 2025 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported a business update and announced financial results for the first quarter ended March 31, 2025 (Press release, Cogent Biosciences, MAY 6, 2025, View Source [SID1234652601]).

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"The first quarter of 2025 was very productive for Cogent as our team focused on executing across our portfolio in preparation for three transformative data readouts this year. We look forward to reporting top-line results from our registration-directed SUMMIT trial with bezuclastinib in patients with nonadvanced systemic mastocytosis in July, followed later in the year with top-line results from our APEX and PEAK trials," said Andrew Robbins, the Company’s President and Chief Executive Officer. "While we are preparing for a potential launch of bezuclastinib in 2026, we are also very proud of the progress we have made with our early-stage pipeline, including presentations from four distinct programs recently at the annual AACR (Free AACR Whitepaper) conference."

Recent Business Highlights

Announced expanded clinical results from the Open Label Extension (OLE) portion of the Company’s ongoing SUMMIT trial evaluating bezuclastinib in patients with nonadvanced systemic mastocytosis (NonAdvSM) at the 2025 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI) meeting.
Bezuclastinib showed a 65% mean improvement in Total Symptom Score (TSS) at 48 weeks, including 88% of patients achieving at least a 50% reduction in TSS.
The safety profile for bezuclastinib remains favorable, with adverse events reported primarily as low-grade and reversible. No treatment-related bleeding or cognitive impairment was observed. The most common treatment-related adverse events were hair discoloration and transient elevations in liver transaminases. All cases of elevated transaminases were asymptomatic and fully reversible.
Presented updated preclinical data from the company’s KRAS, PI3Kα, FGFR2/3 and ErbB2 candidates at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) annual meeting.
Upcoming Milestones

Announce top-line results from SUMMIT in July 2025. SUMMIT is a registration-directed, randomized, double-blind, placebo-controlled, global, multicenter, clinical trial of bezuclastinib in patients with NonAdvSM.
Announce top-line results from APEX in the second half of 2025. APEX is a registration-directed, global, open-label trial in patients with advanced systemic mastocytosis (AdvSM).
Announce top-line results from PEAK by the end of 2025. PEAK is a global, blinded, randomized Phase 3 clinical trial studying the combination of bezuclastinib and sunitinib versus sunitinib alone in patients with imatinib-resistant gastrointestinal stromal tumors (GIST).
First Quarter 2025 Financial Results

Cash and Cash Equivalents: As of March 31, 2025, cash, cash equivalents and marketable securities were $245.7 million. During the quarter, the Company sold shares under the Company’s at-the-market (ATM) stock offering for net proceeds of $24.3 million and incurred a non-recurring payment of $9.6 million related to annual performance-based bonus compensation. Based on its current plans, the Company expects its existing cash, cash equivalents and marketable securities will be sufficient to fund its operating expenses and capital expenditure requirements into late 2026, including through clinical readouts from ongoing SUMMIT, PEAK, and APEX registration-directed trials.

R&D Expenses: Research and development expenses were $63.0 million for the first quarter of 2025 compared to $52.7 million for the first quarter of 2024. The increase was primarily due to costs incurred to support our on-going SUMMIT, PEAK and APEX clinical trials and to the continued progression of our early stage, preclinical and discovery programs. R&D expenses include non-cash stock compensation expense of $5.3 million for the first quarter of 2025 as compared to $4.4 million for the first quarter of 2024.

G&A Expenses: General and administrative expenses were $11.9 million for the first quarter of 2025 compared to $9.7 million for the first quarter of 2024. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $4.8 million for the first quarter of 2025 as compared to $5.0 million for the first quarter of 2024.

Net Loss: Net loss was $72.0 million for the first quarter of 2025 compared to a net loss of $58.3 million for the first quarter of 2024.