On January 18, 2024 Coherus BioSciences, Inc. (Coherus, Nasdaq: CHRS), reported data from the lead-in portion of the Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-targeting antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (uHCC) (Press release, Coherus Biosciences, JAN 18, 2024, View Source [SID1234639325]). These data are being presented at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place January 18-20, 2024 at Moscone West in San Francisco, California. Interleukin (IL)-27 is an immunoregulatory cytokine involved in suppressing anti-tumor immune responses and an important new target for cancer treatment. Casdozo is a first-in-class antibody, and the only clinical stage immunomodulatory cytokine antagonist targeting IL-27.

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"Doublet immunotherapy combinations for the treatment of liver cancer have improved outcomes for patients for whom surgery is not an option or whose cancer has spread. However, not all patients respond to current therapy and novel treatment options that can further improve survival without added toxicity are needed," said Daneng Li, M.D., Associate Professor in the Department of Medical Oncology & Therapeutics Research and Co-Director, Liver Cancer Collaborative Program, City of Hope Comprehensive Cancer Center. "The addition of casdozo to standard of care is encouraging and supports further evaluation of cazdozo, and its novel anti-IL-27 mechanism, as part of triplet therapy in HCC. Additionally, each person with advanced HCC is unique with respect to their tumor, co-morbidities and other factors – the biomarker data showing an association of IL-27 biology and response to casdozo is particularly interesting and the potential to identify biomarkers of response would be an important benefit to patients with liver cancer."

"These impressive early clinical and immune activation data for casdozo in HCC demonstrating an ORR of 38%, including 3 complete responses, and a favorable safety profile add to the growing body of data supporting IL-27 as a promising novel target in combination therapy for advanced solid tumors," said Rosh Dias, M.D., Coherus’ Chief Medical Officer. "We now have data across several tumor types for casdozo demonstrating clinical activity. Our comprehensive clinical development program of ongoing and planned clinical trials including casdozokitug in combination with our anti-PD-1 antibody backbone of toripalimab-tpzi, will further advance our internal next-generation immuno-oncology combinations focused on overcoming immune suppression in the tumor microenvironment with the goal of extending survival and improving outcomes for patients."

Lead-in portion of Phase 2 clinical trial design
The open-label lead-in portion of the Phase 2 clinical trial evaluated casdozo in combination with atezo and bev in 30 patients with treatment-naïve uHCC. Patients received casdozo 10 mg/kg IV q3w, in combination with atezo (1200 mg) and bev (15 mg/kg). The primary endpoint of the lead-in portion of the study was safety and tolerability. Key secondary endpoints included progression-free survival (PFS) and overall response rate (ORR) based on investigator review per RECIST v1.1 (primary) and mRECIST (secondary), as well as disease control rate (DCR). Further [Phase 2] clinical development of cazdozo in HCC is planned to evaluate casdozo/toripalimab (anti-PD-1 antibody)/bev.

Lead-in portion of Phase 2 clinical trial data
As of the data cutoff date (November 9, 2023):
Triplet blockade of the IL-27, PD-(L)1 and VEGF pathways with casdozo/atezo/bev has an acceptable safety profile to date with promising antitumor activity in IO naïve HCC.

Triplet combination treatment was well tolerated with side effect profile consistent with known adverse event (AE) profiles of atezo/bev.
Encouraging early activity with casdozo/atezo/bev:
RECIST v1.1: ORR of 38% (n=29) with 11 durable objective responses including 3 complete responses and 8 partial responses (1 unconfirmed); median progression-free survival of 8.1 months and disease control rate of 58.6%.
mRECIST: ORR of 43% (n=28) with 12 durable objective responses including 3 complete responses and 9 partial responses (1 unconfirmed); median progression-free survival not reached and disease control rate of 60.7%.
Further analyses of samples from patients who responded to treatment (small n) indicate preliminary association between response and biomarkers of IL-27.
These results support continued evaluation of casdozo with VEGF and PD-(L)1 blockade in HCC. Coherus plans to evaluate the combination of casdozo/toripalimab-tpzi(Coherus’ anti-PD-1 antibody)/bev in future clinical trials.

Poster presentation details:
Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VegF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab (atezo) and bevacizumab (bev) in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC)
Poster Board number: B15
Abstract number: 470
Date and Time: Friday, January 19, 2024, 12:30 – 2:00 pm PT
Presenter: Daneng Li, MD
Location: Level 1, West Hall, Moscone West

About Casdozokitug
Casdozokitug is a first-in-class human anti-IL-27 antibody designed to inhibit the activity of this immunosuppressive cytokine. Particular tumor types have been identified where IL-27 appears to play an important role in the immunosuppressive tumor microenvironment and may contribute to resistance to treatment with checkpoint inhibitors. Blocking IL-27 with casdozokitug in clinical trials has led to monotherapy tumor growth inhibition and partial responses in patients with non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) (NCT04374877). An ongoing trial is studying combinations with PD-(L)1 pathway blockade in NSCLC and a planned clnical trial will study the triplet combination of IL-27, PD-(L)1 and VEGF pathway blockade in hepatocellular carcinoma (HCC). Casdozokitug has been granted Orphan Drug designation and Fast Track designation for the treatment of refractory hepatocellular carcinoma from the FDA. It is the first IL-27 antibody to enter the clinic.

On January 18, 2024 BridgeBio Pharma, Inc. (Nasdaq: BBIO) (BridgeBio or the Company), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported strategic financing from Blue Owl Capital (Blue Owl) and Canada Pension Plan Investment Board (CPP Investments), through a wholly owned subsidiary (CPPIB Credit) of CPPIB Credit Investments Inc., bringing in capital of up to $1.25 billion (Press release, BridgeBio, JAN 18, 2024, View Source [SID1234639324]).

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With these transactions, BridgeBio obtains financing from experienced healthcare investors who share the Company’s confidence in the anticipated launch of acoramidis as the potential backbone of therapy for transthyretin amyloid cardiomyopathy (ATTR-CM).

"We are excited to be working with a distinguished group of life sciences investors who are aligned with our view of acoramidis’ blockbuster market opportunity," said Brian Stephenson, Ph.D., CFA, Chief Financial Officer of BridgeBio. "Our newly strengthened balance sheet will enable us to serve ATTR-CM patients with a well-resourced launch of acoramidis, as well as patients with genetic diseases more broadly with multiple Phase 3 readouts for blockbuster indications anticipated over the next few years. Our increasing patient impact should allow us to diversify drivers of top line revenue in the near term and enable reinvestment into R&D paired with opportunistic business development."

The overall collaboration includes the following key features:

A royalty agreement with Blue Owl and CPPIB Credit:
$500 million cash payment upon FDA approval of acoramidis to help support the Company’s commercial launch in exchange for future royalties of 5% of worldwide net sales of acoramidis, both of which are subject to various conditions. This consists of $300 million from Blue Owl and $200 million from CPPIB Credit
Total royalty payments are capped at 1.9 times the invested capital, and the royalty agreement includes investment features (such as change of control provisions that apply prior to FDA approval) intended to provide broad strategic flexibility for BridgeBio going forward
A refinancing with Blue Owl of BridgeBio’s existing senior credit facility:
$450 million of committed capital funded at close to refinance BridgeBio’s existing senior credit facility, extending maturity from 2026 to 2029 and providing the Company with considerable operational flexibility
An additional tranche of up to $300 million, funded at the Company and Blue Owl’s mutual consent to support strategic corporate development activities
"Blue Owl is well-positioned to provide bespoke and scaled financing solutions to the most consequential companies in the life sciences sector," said Sandip Agarwala, Managing Director at Blue Owl Capital. "Acoramidis has demonstrated an impressive and differentiated clinical profile, and we believe it will be an important advancement in the treatment of ATTR-CM. Further, BridgeBio’s promising pipeline of late-stage targeted rare disease therapies address critical unmet needs in these underserved populations. We are pleased to support BridgeBio in its mission of bringing breakthrough medicines to patients."

"This investment in BridgeBio represents an opportunity to provide structured capital solutions to an innovative company in the healthcare space and leverage CPP Investments’ deep capabilities in life sciences," said David Colla, Managing Director and Head of Capital Solutions, CPP Investments. "Investments in leading therapies also help to diversify our capital allocations to income streams that are typically uncorrelated to the broader capital markets."

Morgan Stanley & Co. LLC acted as sole structuring agent on the transactions. Latham & Watkins served as legal advisor to BridgeBio and Cooley LLP advised Blue Owl.

On January 18, 2024 AskGene Pharma Inc. reported encouraging clinical results for ASKB589, an anti-CLDN18.2 antibody, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancer Symposium (ASCO-GI 2024) in San Francisco on January 18-20, 2024 (Press release, AskGene Pharmaceuticals, JAN 18, 2024, View Source [SID1234639323]).

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The results were from clinical trial NCT05632939, a Phase Ib/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, and anti-tumor activities of ASKB589 in combination with chemotherapy (CAPOX) and a PD-1 inhibitor as a first-Line treatment in patients with locally advanced, relapsed and metastatic gastric (G) or gastroesophageal junction (GEJ) adenocarcinoma. As of December 20, 2023, a total of 62 patients with positive CLDN18.2 expression were dosed Q3W with ASKB589 combined with CAPOX and PD-1 inhibitor: 9 patients received ASKB589 at 6 mg/kg (n=3) and 10 mg/kg (n=6) in the dose escalation and 53 patients at 6 mg/kg in the dose expansion. Most of the enrolled patients had moderate to high CLDN18.2 expression (83.9%) and PD-L1 CPS ³1 (59.7%).

ASKB589 was safe and tolerated at both 6 and 10 mg/kg. No dose-limiting toxicity was observed, and maximum tolerated dose (MTD) was not identified during the escalation phase of the study. Most adverse events (AEs) were of mild severity (grade 1 or 2). The most common AEs were hypoalbuminemia (77.4%), nausea (66.1%), anemia (56.5%), neutrophil count decreased (54.8%), and vomiting (51.6%). No patients discontinued the treatment due to AEs.

Among 45 CLDN18.2 moderate to high patients (determined by a validated proprietary companion diagnostic kit) with measurable disease and at least one post-treatment tumor assessment in the 6 mg/kg dose- expansion phase, 36 (80.0%) patients achieved partial response and 9 (20.0%) achieved stable disease as the best overall tumor response per RECISTv1.1. Disease control rate was 100%. As of the cutoff date, 41(77.3%) out of the 53 patients in the dose expansion group were still on treatment.

In summary, ASKB589 plus CAPOX and PD-1 inhibitor as a first-line treatment in patients with G/GEJ cancer demonstrated good safety and tolerability. Adding a PD-1 inhibitor to ASKB589 plus CAPOX in patients with moderate to high CLDN18.2 expression resulted in encouraging anti-tumor activities with deep and durable responses. Based on the interim results of this study, NMPA greenlighted the Phase 3 study of ASKB589 in combination with CAPOX and PD-1 inhibitor as a first-line treatment in CLDN18.2 moderate to high (≥40% 2+/3+ staining) patients with advanced G/GEJ cancer in China.

Jian-Feng (Jeff) Lu, Ph.D., CEO of AskGene, commented: "Claudin 18.2 has recently been validated as a new molecular target that demonstrates clinical benefit for patients with gastric and gastroesophageal cancer. Our study shows that triple combination of ASKB589, chemotherapy, and PD-1 inhibitor can be administered safely in patients and results in a very high rate of deep and durable responses, as well as a 100% disease control rate. We have initiated the registrational trial and expect to enroll the first patient soon".

Presentation Details

Title: A Phase Ib/II Study of ASKB589 (Anti-CLDN18.2 Monoclonal Antibody) in Combination with CAPOX and PD-1 Inhibitor as a First-Line Treatment of Locally Advanced, Relapsed and Metastatic G/GEJ Cancer (NCT05632939)
Principle Investigator: Dr. Lin Shen, Peking University Cancer Hospital
Presenter: Dr. Zhi Peng, Peking University Cancer Hospital
Abstract #: 317
Poster #: E17
About NCT05632939

The NCT04632108 study is a Phase Ib/II, two-part, dose escalation and expansion study to evaluate the safety, tolerability, and anti-tumor activities of ASKB589 in combination with chemotherapy (CAPOX) and a PD-1 inhibitor as a first-Line treatment in patients with locally advanced, relapsed and metastatic G/GEJ cancer. The study includes ASKB589 dose escalation (6 and 10 mg/kg) and expansion study of ASKB589 (6 mg/kg) combined with CAPOX and PD-1 inhibitor. Patients with positive CLDN18.2 expression (any tumor cell with ≥1+ membrane staining) determined by the central lab have been enrolled.

About ASKB589

ASKB589 is an innovative biological drug discovered and developed by AskGene. It is a recombinant humanized monoclonal antibody targeting CLDN 18.2. The drug mediates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) through high-affinity binding to CLDN18.2-expressing cancer cells. ASKB589 is intended for treatment of G/GEJ cancer, pancreatic cancer, and additional cancer types which express CLDN18.2.

On January 18, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported that the US FDA have cleared Amplia’s IND application for a trial of Amplia’s best-in-class focal adhesion kinase (FAK) inhibitor narmafotinib in pancreatic cancer (Press release, Amplia Therapeutics, JAN 18, 2024, View Source [SID1234639295]). The proposed trial will explore the safety, tolerability and efficacy of a combination of narmafotinib with the chemotherapy regime FOLFIRINOX.

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The company is currently undertaking a Phase 2a clinical trial of narmafotinib, in combination with two chemotherapy drugs, gemcitabine and Abraxane, in advanced pancreatic patients in Australia and South Korea. In contrast, the IND application reviewed by the US Food and Drug Administration (FDA) supports the use of narmafotinib in combination with a different chemotherapy called FOLFIRINOX (a four drug regimen), which is widely employed in the US for the treatment of pancreatic cancer.

The IND document is an extensive dossier that details all preclinical and clinical data amassed to date for narmafotinib, along with complete CMC (chemistry, manufacturing and controls) information. The final document comprised more than 10,000 pages and represented a major undertaking by the company over the previous months.

Amplia CEO and MD Dr Chris Burns commented: "Clearance of the IND by the US FDA is a significant step forward for the Company. We will now start planning the combination trial of narmafotinib with FOLFIRINOX in the US, which expands the clinical opportunities for our best-in-class FAK inhibitor. FOLFIRINOX is the preferred treatment for pancreatic patients in the USA and most of Europe, and therefore this combination trial is highly relevant as we position narmafotinib as the preferred drug to enhance the effectiveness of existing chemotherapy combinations in pancreatic cancer."

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics.

On January 17, 2024, Alector, Inc. (the "Company") entered into an underwriting agreement (the "Underwriting Agreement") with Cantor Fitzgerald & Co. (the "Underwriter"), relating to the issuance and sale (the "Offering") of 10,869,566 shares of the Company’s common stock, par value $0.0001 per share, at a price per share of $6.57 to be paid by the Underwriter (the "Underwritten Shares") (Filing, Alector, JAN 17, 2024, View Source [SID1234640081]). The Company also granted the Underwriter an option exercisable for 30 days from the date of the Underwriting Agreement to purchase up to an additional 1,630,434 shares of common stock (together with the Underwritten Shares, the "Shares"). All of the Shares in the Offering are being sold by the Company.

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The gross proceeds from the Offering are expected to be approximately $75 million before deducting underwriting discounts and commissions and estimated offering expenses payable by the Company and assuming no exercise of the Underwriter’s option to purchase additional shares. The Offering is expected to close on January 19, 2024, subject to the satisfaction of customary closing conditions.

The Underwriting Agreement contains customary representations, warranties, and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Underwriter, including for liabilities under the Securities Act of 1933, as amended, other obligations of the parties, and termination provisions. The representations, warranties, and covenants contained in the Underwriting Agreement were made only for purposes of such agreement and as of specific dates, were solely for the benefit of the parties to such agreement, and may be subject to limitations agreed upon by such parties.

The Offering is being made pursuant to the Company’s effective registration statement on Form S-3 (File No. 333-270126) (the "Registration Statement"), which was declared effective by the Securities and Exchange Commission (the "Commission") on May 1, 2023, and a related prospectus and prospectus supplement, each as filed with the Commission.

The above summary of the Underwriting Agreement does not purport to be complete and is qualified in its entirety by reference to the Underwriting Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. The legal opinion of Wilson Sonsini Goodrich & Rosati, Professional Corporation relating to the shares of common stock being offered pursuant to the Underwriting Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K.