On October 12, 2023 SystImmune, Inc (SystImmune), a clinical-stage biopharmaceutical company, reported that the first patient was treated on October 10th, 2023 with BL-B01D1, a first-in-class bispecific antibody-drug conjugate targeting both EGFR and HER3, as part of the global, multi-center Phase 1 study, BL-B01D1-LUNG-101, that is underway to evaluate the safety, tolerability, and efficacy of BL-B01D1 in individuals with Metastatic or Unresectable Non-Small Cell Lung Cancer (NSCLC) (Press release, SystImmune, OCT 12, 2023, View Source [SID1234635906]). The study, anticipated to enroll around 100 participants, includes two dosing schedules (Cohort A and Cohort B) and three phases (dose escalation, dose finding, and dose expansion).

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"This study underscores our commitment to advancing medical science and improving the lives of those affected by NSCLC. We look forward to the results of BL-B01D1-LUNG-101 in diverse populations and its potential impact on NSCLC care," stated Dr. Martin S. Olivo, Chief Medical Officer at SystImmune.

This registered study is titled "A Phase 1 Study Evaluating the Safety, Tolerability, and Efficacy of BL-B01D1 in Subjects with Metastatic or Unresectable Non-Small Cell Lung Cancer," and this research represents a significant step forward in NSCLC treatment possibilities. NCT05983432

About BL-B01D1

BL-B01D1 is a first-in-class bispecific antibody-drug conjugate (ADC) developed by SystImmune, targeting both EGFR and HER3, proteins that are highly expressed in most epithelial tumors. The tetravalent BL-B01D1 possesses two binding domains blocking each Growth Factor Receptor, which both drive cancer cell proliferation and survival. Inheriting the SI-B001 mechanisms of action, BL-B01D1 effectively blocks EGFR and HER3 signals to cancer cells, thereby reducing proliferation and survival signals. Upon antibody-mediated internalization, BL-B01D1 is trafficked to cancer cell lysosomes and liberates its therapeutic payload that induced genotoxic stress activating pathways leading to cancer cell death.

The two targets of BL-B01D1 are broadly expressed in epithelial tumors, including NSCLC, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Gastrointestinal tumors, Gynecological tumors, and others. The therapeutic conjugated toxin of BL-B01D1 comprises SystImmune’s Ex-0115 linker-payload platform, a proprietary Top1 inhibitor conjugated to the bi-specific antibody by a stable, cleavable linker. Each BL-B01D1 carries 7-8 units of SystImmune’s proprietary ED-04 toxin.

On October 12, 2023 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported that its partner Asieris Pharmaceuticals (SSE: 688176) has today unveiled the results of its Hexvix (APL-1706) Phase III clinical trial in China (Press release, PhotoCure, OCT 12, 2023, View Source [SID1234635905]). A presentation scheduled for today at the 43rd Congress of the Société Internationale d’Urologie (SIU), confirms that, in a Chinese population, Hexvix blue light cystoscopy (BLC) outperformed white light cystoscopy (WLC) in the detection of bladder cancer, particularly in cases of carcinoma in situ (CIS), and exhibited good tolerability.

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The highly statistically significant results corroborate the findings of Photocure’s own randomized controlled trials (RCTs) that demonstrate the clinical benefits of Hexvix BLC over WLC, specifically superior tumor detection and a favorable tolerability profile with no serious adverse events. Moreover, Asieris’ Phase III Hexvix trial is the first RCT conducted with high definition 4K blue light capital equipment.

"This randomized-controlled trial reinforces the benefits of BLC with Hexvix in tumor detection over WLC alone with clinically convincing and statistically significant results. This is on the backdrop of this Chinese trial being the first RCT conducted with 4K high definition (HD) blue light equipment, making it a valuable addition to the body of evidence already available on BLC with Hexvix. It confirms that BLC with Hexvix is additive to WL also with high quality HD imaging technology. We are pleased to see and acknowledge that our partners at Asieris are driving innovation to support unmet needs in bladder cancer", said Anders Neijber, Photocure’s Chief Medical Officer.

The trial results have been selected as a "late-breaking abstract" at the 43rd Congress of the Société Internationale d’Urologie (SIU) in Istanbul, Turkey, October 11-14. The clinical study data will be presented today, October 12, in the form of an Oral ePoster at 1:45pm local time.

The study is a prospective, self-controlled, multicenter Phase Ⅲ study intended to evaluate the safety and detection benefits of blue light cystoscopy (BLC) with Hexvix compared to white light cystoscopy (WLC) in the diagnosis of non-muscle invasive bladder cancer (NMIBC) in a Chinese population. The study included a total of 158 patients, of which 114 underwent BLC. Of the 97 patients diagnosed with NMIBC, a total of 42 patients (43.3%) had one or more additional lesions detected with Hexvix BLC compared to WLC (p<0.0001). Among the 114 patients, 11.4% (13/114) had CIS lesions, and among these, 11 patients (84.6%, 11/13) had additional CIS lesions detected under Hexvix BLC that were not found under WLC. The detection rates for PUNLMP, CIS, Ta, T1, and T2-T4 tumor lesions in the BLC group were NA, 94.7%, 100%, 98.2%, and 100%, respectively, while in the WLC group, they were NA, 42.1%, 76.1%, 91.2%, and 100%, respectively.

Read Asieris’ full media release here: View Source

Asieris Pharmaceuticals is a global biopharma company specializing in discovering, developing and commercializing innovative drugs for the treatment of genitourinary tumors and other related diseases.

In January 2021, Asieris entered into a license agreement with Photocure ASA to obtain the exclusive registration and commercialization rights of Hexvix in mainland China and Taiwan.

Note to editors:

All trademarks mentioned in this release are protected by law and are registered trademarks of Photocure ASA.

This press release may contain product details and information which are not valid, or a product is not accessible, in your country. Please be aware that Photocure does not take any responsibility for accessing such information which may not comply with any legal process, regulation, registration or usage in the country of your origin.

About Bladder Cancer

Bladder cancer ranks as the 8th most common cancer worldwide – the 5th most common in men – with 1 720 000 prevalent cases (5-year prevalence rate)1a, 573 000 new cases and more than 200 000 deaths in 2020.1b

Approx. 75% of all bladder cancer cases occur in men.1 It has a high recurrence rate with up to 61% in year one and up to 78% over five years.2 Bladder cancer has the highest lifetime treatment costs per patient of all cancers.3 Bladder cancer is a costly, potentially progressive disease for which patients have to undergo multiple cystoscopies due to the high risk of recurrence. There is an urgent need to improve both the diagnosis and the management of bladder cancer for the benefit of patients and healthcare systems alike. Bladder cancer is classified into two types, non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), depending on the depth of invasion in the bladder wall. NMIBC remains in the inner layer of cells lining the bladder. These cancers are the most common (75%) of all BC cases and include the subtypes Ta, carcinoma in situ (CIS) and T1 lesions. In MIBC the cancer has grown into deeper layers of the bladder wall. These cancers, including subtypes T2, T3 and T4, are more likely to spread and are harder to treat.4

1 Globocan. a) 5-year prevalence / b) incidence/mortality by population. Available at: View Source today, accessed [January 2022].
2 Babjuk M, et al. Eur Urol. 2019; 76(5): 639-657
3 Sievert KD et al. World J Urol 2009;27:295–300
4 Bladder Cancer. American Cancer Society. View Source

About Hexvix/Cysview (hexaminolevulinate HCl)

Hexvix/Cysview is a drug that preferentially accumulates in cancer cells in the bladder, making them glow bright pink during Blue Light Cystoscopy (BLC). BLC with Hexvix/Cysview, compared to standard white light cystoscopy alone, improves the detection of tumors and leads to more complete resection, fewer residual tumors, and better management decisions.

Cysview is the tradename in the U.S. and Canada, Hexvix is the tradename in all other markets. Photocure is commercializing Cysview/Hexvix directly in the U.S. and Europe and has strategic partnerships for the commercialization of Hexvix/Cysview in China, Chile, Australia, New Zealand and Israel. Please refer to View Source for further information on our commercial partners.

On October 12, 2023 Asieris Pharmaceuticals (Stock Code: 688176.SH), a global biopharma company specializing in discovering, developing and commercializing innovative drugs for the treatment of genitourinary tumors and other related diseases, reported that it has unveiled its phase III clinical trial data for APL-1706 (Hexvix), an imaging drug used for the diagnosis or surgery of bladder cancer, at the 43rd Congress of the Société Internationale d’Urologie (SIU) in 2023 (Press release, Asieris Pharmaceuticals, OCT 12, 2023, View Source [SID1234635904]). The study confirmed that, in the Chinese patient, APL-1706 in combination with blue light cystoscopy (BLC) outperformed white light cystoscopy (WLC) in the detection of bladder cancer, particularly in cases of carcinoma in situ (CIS), and exhibited good tolerability.

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The study included a total of 158 patients, with 37 patients in the training cases group. Six patients were randomly assigned to the standard WLC control group, and one patient dropped out, leaving 114 patients in the full analysis set (FAS). Among the 97 patients diagnosed with Ta, T1, and CIS (mFAS), compared to standard WLC, a total of 42 patients (43.3%) detected one or more additional bladder cancer lesions through the combination of APL-1706 and blue light cystoscopy (p<0.0001). Among the 114 patients, 13 patients (11.4% ,13/114) had CIS lesions, and among these, 11 patients (84.6%, 11/13) had additional CIS lesions detected under BLC that were not found under WLC. The detection rates for PUNLMP, CIS, Ta, T1, and T2-T4 tumor lesions in the BLC group were NA, 94.7%, 100%, 98.2%, and 100%, respectively, while in the WLC group, they were NA, 42.1%, 76.1%, 91.2%, and 100%, respectively. The false positive rates for BLC and WLC were 23.2% and 16.0%, respectively. A total of 95 patients reported 200 adverse events, all of which were mild to moderate, with 95.5% of them unrelated to APL-1706. There were no serious adverse events reported.

Dr. Linda Wu, Chief Development Officer of Asieris Pharmaceuticals, said, "APL-1706 is currently the only approved optical imaging for assisting in the diagnosis and surgery of bladder cancer worldwide. The data presented at the SIU conference further validates the tremendous clinical value of APL-1706. We believe that this innovative drug will bring significant benefits to bladder cancer patients in the local market. We will actively advance the related regulatory submissions in China, expediting its market entry to benefit more patients as soon as possible."

In January 2021, Asieris entered into a license agreement with Photocure ASA (Photocure, OSE:PHO), a bladder cancer specialty company based in Oslo, Norway, and obtained the exclusive registration and commercialization rights of Hexvix in mainland China and Taiwan.

On October 12, 2023 Avenge Bio, Inc. ("Avenge"), a clinical stage, oncology-focused biotechnology company developing the LOCOcyte Immunotherapy platform for the precision administration of potent immune effector molecules to treat solid tumors, reported participation in the upcoming investor conference (Press release, Avenge Bio, OCT 12, 2023, View Source [SID1234635903]).

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3rd Annual Needham Private Biotech Company Virtual 1×1 Forum
Date & Time: October 17-18, 2023

In September 2023, Avenge Bio received FDA Fast Track designation for AVB-001. AVB-001 is an encapsulated cell product engineered to produce native human interleukin-2 (hIL-2) and is delivered intraperitoneally (IP) to patients. Avenge is currently enrolling patients in a First-in-Human, Phase 1/2, multicenter clinical trial (NCT05538624) designed to evaluate the safety and efficacy of AVB-001. The Company has advanced through multiple dose levels in a dose escalation cohort and expects to initiate a Phase 2 dose expansion trial in 1H 2024.

On October 12, 2023 Nested Therapeutics, a biotechnology company pioneering a next-generation precision medicine platform to address hard-to-treat cancers, reported the first preclinical data from its lead candidate, NST-628, a mechanistically novel non-degrading molecular glue that targets multiple nodes in the RAS/MAPK pathway, outlined in three poster presentations at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference taking place in Boston, Massachusetts from October 11-15, 2023 (Press release, Nested Therapeutics, OCT 12, 2023, View Source [SID1234635902]).

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NST-628 outperformed other MAPK-targeted compounds administered as either single agents or combinations in anti-tumor activity and tolerability. Additionally, NST-628 effectively crossed the blood-brain barrier, suggesting a potential advantage for the treatment of brain metastases and primary CNS malignancies with MAPK pathway alterations.

"Taken together, these superior preclinical data suggest that NST-628 could offer a potential first-in-class treatment in the current RAS/MAPK inhibitor space, supporting its advancement into first-in-human clinical trials," said Darrin Miles, Chief Executive Officer of Nested Therapeutics. "We understand the need to bring more effective treatment options that have the ability to overcome the intrinsic mechanisms that tumor cells evolve to become resistant to cancer therapies, and we look forward to initiating our Phase 1 study in patients in the first half of 2024."

NST-628 is being developed through a robust biophysical and cellular characterization to leverage proprietary structural insights of how signaling complexes form and function in cancer. The compound acts through a defined mechanism of action that could address common pitfalls of other MAPK-targeted compounds, which remain unable to circumvent the risk of intrinsic resistance via signaling pathway reactivation.

Key takeaways from the posters are as follows:

NST-628 is a novel molecular glue that inhibits signaling and pathway reactivation in oncogenic RAS-MAPK cancers (Abstract Number: A086)

NST-628 bound to CRAF-MEK, BRAF-MEK, ARAF-MEK complexes were structurally characterized using x-ray crystallography and cryogenic electron microscopy (cryo-EM). Increased stabilization of the CRAF-MEK complex by NST-628 was observed and may contribute to the decreased pathway reactivation in specific biomarker-driven tumors.
NST-628 is a potent, best-in-class MAPK pathway molecular glue that inhibits RAS- and RAF-driven cancers (Abstract Number: A088)

NST-628 demonstrated strong efficacy and tolerability across multiple tumor types with RAS-MAPK alterations, including melanoma, lung, and pancreatic animal models.
The predicted effective human half-life is amenable to daily dosing in the clinic, supporting best-in-class potential for NST-628.
NST-628 is a potent, fully brain-penetrant, RAS/MAPK pathway molecular glue inhibitor with efficacy in CNS tumor models (Abstract Number: A089)

Currently approved inhibitors of the RAS-MAPK pathway have limited CNS exposure, and NST-628 demonstrates full CNS permeability far higher than trametinib or VS-6766.
NST-628 leads to dose-dependent inhibition of the MAPK pathway in murine brain tissue, along with tumor regressions observed with a daily dosing regimen.
Nested Therapeutics plans to submit an IND for NST-628 following completion of ongoing preclinical and IND-enabling studies, to support first-in-human studies to start in the first half of 2024.

About DeCRYPTion Platform

Nested Therapeutics’ DeCRYPTion Platform is a purpose-built, insightful drug discovery platform that enables Nested to identify new, overlooked areas of opportunity in the form of high value targets and design therapeutics for a perfect fit. The platform includes three critical components: (1) mapping mutational clusters onto the structural proteome, (2) identifying druggable pockets and cancer-driving mechanisms, and (3) designing novel drugs optimized for the druggable pocket.