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National Medical Products Administration (NMPA) Approves Chipscreen Bioscience’s Chidamide (Epidaza) combined with R-CHOP for the treatment of diffuse large B-cell lymphoma

On April 30, 2024 Shenzhen Chipscreen Biosciences Co., Ltd. (Chipscreen Biosciences, Stock Symbol: 688321.SH) reported that the company’s lead innovative product Chidamide (Epidaza) , an oral subtype-selective histone deacetylase (HDAC) inhibitor, combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), has been officially approved by the National Medical Products Administration (NMPA) for treatment of previously untreated diffuse large B-cell lymphoma (DLBCL) with positive MYC and BCL2 expression (Press release, Shenzhen Chipscreen Biosciences, APR 30, 2024, View Source [SID1234642479]). Up to now, Chidamide has been approved for multiple indications globally. (For more information, please review the global commercialization situation).

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Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, with approximately 30000 new cases occurring annually in China. Clinical diagnosis and treatment guidelines and consensus both domestically and internationally recommend the R-CHOP regimen as the standard first-line treatment for DLBCL. However, about one-third or more of patients in the overall population still experience ineffective or early recurrence of first-line R-CHOP treatment. Meanwhile, approximately 30% of patients with DLBCL exhibit simultaneous overexpression of MYC/BCL2 protein (referred to as "double expression" lymphoma, DEL), and their efficacy and prognosis after R-CHOP treatment are significantly lower than those of non double expression patients. Therefore, how to combine new drugs based on R-CHOP regimen to provide a more effective and safer treatment to our patients is a significant unmet medical need.

The approval of this new indication is based on a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial DEB trial (NCT04231448). The DEB trial is the first Phase III registered clinical study in the world as first line treatment of MYC/BCL2 dual expression diffuse large B-cell lymphoma. This trial is to evaluate the efficacy and safety of Chidamide combined with R-CHOP compared to R-CHOP in primary treatment and MYC/BCL2 dual expression DLBCL subjects. Based on the interim analysis conducted by the Independent Data Monitoring Committee (iDMC), the efficacy and safety indicators set by the protocol were achieved. Compared with the R-CHOP regimen, the Chidamide combination regimen significantly improved the complete response rate (CRR) of the study’s key secondary endpoint, and the study’s primary endpoint, event free survival (EFS), also showed a clear trend of benefit. The experimental safety profile is consistent with known risks, and no new significant safety signals were found. The results of the interim analysis of the DEB Phase III study were selected as the Late breaking Abstract (LBA) for the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on April 24, 2024.

Dr. Xianping Lu, Chairman and General Manager of Chipscreen Biosciences, stated, "The classic R-CHOP regimen has been used as a first-line treatment for diffuse large B-cell lymphoma (DLBCL) for nearly 20 years, but its therapeutic effect is not satisfactory in populations with dual expression of BCL2 and MYC proteins. The combination of Chidamide and R-CHOP is the world’s first phase 3 registered clinical study that focuses on first line therapy of dual expressed DLBCL, and also the world’s first R-CHOP improvement study with significant benefits in complete remission rate. We believe that the approval of the new indication will bring new hope and better survival benefits to patients."

About Chidamide (Epidaza)

Chidamide (Tucidinostat, Trade name: Epidaza), a Class 1.1 innovative drug, is a novel molecular entity with global patent protection and the first marketed product developed independently by Chipscreen Biosciences. The first original chemical new drug approved in China, Chidamide is also the first oral subtype-selective histone deacetylase (HDAC) inhibitor in the world, Since its approval in China in December 2014 for the treatment of peripheral T-cell lymphoma, Chidamide has achieved significant commercialization worldwide and continuously explored new indications.

Global commercialization situation:

In December 2014, Chidamide was approved for use in patients with recurrent or refractory peripheral T-cell lymphoma (PTCL) in China;
In November 2019, Chidamide was approved to combine aromatase inhibitors to treat locally advanced or metastatic breast cancer patients with estrogen receptor positive, human epidermal growth factor receptor-2 negative, postmenopausal, and endocrine therapy relapse or progress in China;
In June 2021, Chidamide was approved for monotherapy in the treatment of recurrent or refractory (R/R) adult T-cell leukemia (ATL) in Japan;
In December 2021, Chidamide was approved for monotherapy for recurrent or refractory (R/R) peripheral T-cell lymphoma (PTCL) in Japan;
In March 2023, Chidamide was approved to be used for postmenopausal women with locally advanced or metastatic breast cancer who are hormone receptor positive, type II human epidermal growth factor receptor (HER2) negative, and relapse or worsen after endocrine therapy (in combination with exemestane) in Taiwan, China;
In April 30, 2024, Chidamide was approved to use in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for previously untreated diffuse large B-cell lymphoma (DLBCL) patients with positive MYC and BCL2 expression in China.
Global exploration of other indications:

In addition to ongoing global multicenter phase III clinical trial for the first-line treatment of melanoma in comniation with Opdivo, Chidamide is also conducting multiple clinical trials in China and internationally in combination with different anti-tumor immunotherapies.
In November 2023, the Phase II clinical trial of the first-line treatment of non-small cell lung cancer with Chidamide combined with Tislelizumab was completed and enrolled.
On March 4, 2024, Professor Ruihua Xu and Professor Feng Wang from the Cancer Prevention and Treatment Center of Sun Yat sen University led the research on CAPAbility-01, which was published on the world’s top academic journal Nature Medicine (IF=82.9). As one of the most valuable sub journals under Nature, the publication of Nature Medicine reflects the academic authority’s recognition of CAPAbility-01 research. This study indicates that for patients with microsatellite stable/mismatched repair function intact (MSS/pMMR) type metastatic colorectal cancer (mCRC), a three drug regimen led by Chidamide (Chidamide+sintilimab antibody+bevacizumab) for third line and above treatment, with an 18 week PFS rate of 64.0%, an ORR of 44.0%, and a median PFS of 7.3 months, is considered a promising treatment option for MSS/pMMR advanced CRC patients.
On April 24, 2024, an abstract entitled "Tucidinostat plus R-CHOP in previously untreated diffuse large B-cell lymphoma with double expression of MYC and BCL2: An interim analysis from the phase III DEB study" was selected the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) LBA list for the 2024 ASCO (Free ASCO Whitepaper), which submitted by Professor Weili Zhao’s team from Ruijin Hospital affiliated with Shanghai Jiao Tong University School of Medicine

CIRM Awards $11.8 Million Grant for Clinical Trial in High-Grade Glioma Including Glioblastoma Using DB107, a Novel DGM7™ Genetic Biomarker-Guided Gene Therapy

On April 30, 2024 Denovo Biopharma LLC (Denovo), a pioneer in applying precision medicine to the development of innovative therapies, reported that the California Institute for Regenerative Medicine (CIRM) has awarded a $11.8M grant for further development of DB107, Denovo’s DGM7 biomarker–guided late–stage gene therapy, for high–grade glioma (HGG) including glioblastoma (GBM), a malignant brain cancer (Press release, Denovo Biopharma, APR 30, 2024, View Source;a-novel-dgm7-genetic-biomarker-guided-gene-therapy-302131547.html [SID1234642478]). CIRM has awarded the grant to Dr. Noriyuki Kasahara, MD, PhD, at the University of California San Francisco (UCSF) and a group of investigators at California universities to conduct a Phase 1/2 clinical trial studying DB107 in patients with newly–diagnosed HGG.

The trial, titled "A Phase I/IIa Study to Evaluate the Efficacy of DB107–RRV, Administered to Subjects at Time of Resection and Intravenously Thereafter, in Combination with DB107–FC and Radiation Therapy or DB107–FC, Temozolomide (TMZ) and Radiation Therapy in Patients with Newly–Diagnosed High–Grade Glioma," plans to enroll up to 70 patients. The trial aims to demonstrate improvements in progression–free survival.

DB107 consists of two components: DB107–RRV (vocimagene amiretrorepvec) as a prodrug activator gene therapy and DB107–FC (extended-release 5–fluorocytosine [5–FC]) as an oral prodrug. DB107–RRV, a retroviral replicating vector (RRV) administered intratumorally and intravenously, converts the orally administered 5–FC into the potent chemotherapy agent 5–fluorouracil (5–FU) locally at the tumor sites. This enables intratumoral concentrations 30–50 times of those achievable by 5–FU systemic administration, killing tumor cells while minimizing the systemic exposure and off–target toxicities of 5–FU. Using its proprietary biomarker discovery platform including whole genome sequencing (WGS) and artificial intelligence (AI), Denovo discovered the novel germline genetic biomarker, Denovo Genomic Marker 7 (DGM7), which is located in the SHROOM3 gene intron. Retrospective analysis of an earlier randomized clinical trial in patients with recurrent HGG suggested improved overall survival in DGM7–positive patients treated with DB107.

"We are excited to conduct this novel trial which will be investigating several new approaches for the first time in patients with newly–diagnosed high–grade glioma. In addition to DB107–RRV being administered both intratumorally and intravenously to provide more exposure, this study will also use the RRV in conjunction with radiation therapy and chemotherapy with temozolomide. In addition to the direct therapeutic effect of gene therapy, glioma cells will be sensitized to these standard therapies by 5–FU generated directly within the patient’s tumor from DB107–FC. We are also excited to test the DGM7 biomarker to see if we can identify patients who may benefit the most from this unique gene therapy approach," said Dr. Kasahara.

DGM7 status will be determined at the time of enrollment to prospectively assess the effect of the biomarker on clinical outcomes. The study will be conducted at UCSF (Dr. Noriyuki Kasahara, MD, PhD, and Dr. Nicholas Butowski, MD), University of Southern California (USC) (Dr. Thomas Chen, MD, PhD), and University of California San Diego (UCSD) (Dr. David Piccioni, MD, PhD), and will be managed by Anova Enterprises, Inc.

"We are thrilled to continue the clinical development of our biomarker–guided DB107 gene therapy in patients with HGG including GBM, a major unmet medical need with less than 5% of GBM patients surviving 5 years," said Dr. Matthew A. Spear, MD, Denovo’s Chief Medical Officer and Chief Development Officer. "Alongside our recent announcement of positive results in a Phase 2b clinical trial of our DGM4 biomarker–guided DB104 drug (liafensine) in treatment–resistant depression, the CIRM grant provides continued validation of Denovo’s approach to discovering new genetic biomarkers and developing biomarker–guided therapies."

About HGG and GBM
The most common type of high–grade glioma (HGG) is glioblastoma (GBM), which is also the most common type of adult primary brain cancer, with 18,000 newly–diagnosed patients in the US and 13,000 deaths annually. Standard treatments for patients with newly–diagnosed GBM can include surgery followed by radiation and chemotherapy, but treatment options are limited. The 5–year survival rate of patients with GBM is less than 5%.

About DB107 and the DGM7 Biomarker
DB107 is an investigational combination product consisting of the DB107–RRV (vocimagene amiretrorepvec) gene therapy and DB107–FC (extended–release 5–fluorocytosine) oral prodrug. DB107–RRV, an innovative proprietary retroviral replicating vector (RRV), is combined with DB107–FC to selectively infect and kill cancer cells while stimulating a robust and durable anti–cancer immune response against a tumor with minimal toxicity. DB107 has been tested clinically in solid tumors including recurrent high–grade glioma (rHGG) and colorectal cancer, most recently in a randomized 403–patient Phase 2/3 trial in rHGG including glioblastoma (GBM). Using its proprietary biomarker discovery platform, Denovo discovered the novel genetic biomarker, DGM7, which has been shown to be associated with treatment response to DB107 in patients with rHGG including GBM. DB107 has received Fast Track Designation and Breakthrough Therapy Designation from the FDA, as well as Orphan Drug Designations from the FDA and EMA.

Citius Pharmaceuticals Announces Closing of $15 Million Registered Direct Offering

On April 30, 2024 Citius Pharmaceuticals Inc. (Nasdaq: CTXR) ("Citius" or the "Company"), a late-stage biopharmaceutical company dedicated to the development and commercialization of first-in-class critical care products, reported that it has closed its previously announced registered direct offering for the purchase of an aggregate of 21,428,574 shares of its common stock and accompanying warrants to purchase up to an aggregate of 21,428,574 shares of its common stock, at a purchase price of $0.70 per share and accompanying warrant (Press release, Citius Pharmaceuticals, APR 30, 2024, View Source [SID1234642477]). The warrants have an exercise price of $0.75 per share, will be exercisable six months from the date of issuance, and will expire five years from the initial exercise date.

H.C. Wainwright & Co. acted as the exclusive placement agent for the offering.

The aggregate gross proceeds to the Company from the offering were approximately $15 million, before deducting the placement agent fees and other offering expenses payable by the Company. Citius currently intends to use the net proceeds from the offering for general corporate purposes, including pre-clinical and clinical development of our product candidates and working capital and capital expenditures.

The securities described above were offered pursuant to a "shelf" registration statement (File No. 333-277319) filed with the Securities and Exchange Commission ("SEC") on February 23, 2024 and declared effective on March 1, 2024. The offering was made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. The prospectus supplement and the accompanying prospectus relating to the securities offered was filed with the SEC and is available at the SEC’s website at www.sec.gov. Electronic copies of the prospectus supplement and the accompanying prospectus relating to the securities being offered may also be obtained by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, NY 10022, by telephone at (212) 856-5711 or e-mail at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

Phio Pharmaceuticals Announces Upcoming Presentation at the Annual Meeting of the Society of Clinical Oncology (ASCO)

On April 30, 2024 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a clinical stage biotechnology company whose proprietary INTASYL siRNA gene silencing technology is designed to make immune cells more effective in killing tumor cells, reported it is presenting new data about its lead product candidate, PH-762, an INTASYL compound (Press release, Phio Pharmaceuticals, APR 30, 2024, View Source [SID1234642476]).

PH-762 is currently being studied in a US clinical trial to assess safety and efficacy in specific skin cancers. (NCT 06014086). This open-label Phase 1b clinical study (NCT 06014086) is designed to evaluate the safety and tolerability of neoadjuvant use of IT PH-762 in Stages 1,2 and 4 cutaneous squamous cell carcinoma, Stage 4 melanoma and Stage 4 Merkel cell carcinoma. Stages 1 and 2 cSCC represent 77% of all new cSCC annually. There are no drug products approved for treatment of Stages 1 and 2 cSCC.

The data will be presented at the annual meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) to be held in Chicago, Illinois.

Title: INTASYL PH-762: PD-1 Intratumoral Immunotherapy for Cutaneous Carcinoma

Poster Number: TPS9620
Topic: Melanoma/Skin Cancer
Presenting Author: Mary Spellman, M.D.
Date and Time: June 1, 2024: 1:30-4:30 PM CDT

Sutro Biopharma Announces Initiation of Randomized Portion (Part 2) of REFRαME-O1 Trial

On April 30, 2024 Sutro Biopharma, Inc. (Sutro or the Company) (NASDAQ: STRO), a clinical-stage oncology company pioneering site-specific and novel-format antibody drug conjugates (ADCs), reported that the randomized portion (Part 2) of REFRαME-O1, the registration-directed trial of luveltamab tazevibulin (luvelta) in platinum-resistant ovarian cancer (PROC), is now open for enrollment, and the planned 50 patients in Part 1 of the trial have been enrolled (Press release, Sutro Biopharma, APR 30, 2024, View Source [SID1234642475]). Luvelta is a novel Folate Receptor-α (FRα) targeting ADC with the potential to benefit 8 out of 10 PROC patients, including addressing high unmet medical need in patients with low-medium FRα expression.

"We are pleased to announce the initiation of the Phase 3 portion of our global, registration-directed clinical trial of luvelta, in patients with platinum-resistant ovarian cancer," said Anne Borgman, M.D., Sutro’s Chief Medical Officer. "The speed with which we were able to enroll Part 1 of the trial speaks to the continued demand for a targeted therapy for patients that are not well supported by the standard of care. With evidence of clinical activity seen in all tumor types that have been tested with luvelta, we look forward to providing a promising treatment option to patients in need, including those with ovarian cancer and beyond."

REFRaME-O1 is a global registration-directed study evaluating the efficacy and safety of luvelta versus chemotherapy in women with PROC with FRα expression ≥25% Tumor Proportion Score (TPS), defined as at least 25% or greater of tumor expressing FRα, at any intensity (1+,2+,3+). In Part 2, approximately 500 patients will be enrolled and randomized 1:1 to the selected luvelta dose or investigators’ choice of chemotherapy. The trial includes a planned interim analysis to support a potential application for accelerated approval.

About Luveltamab Tazevibulin
Luveltamab tazevibulin, abbreviated as "luvelta" and formerly known as STRO-002, is a FRα-targeting antibody-drug conjugate (ADC) designed to treat a broad range of patients with ovarian cancer, including those with lower FRα-expression who are not eligible for approved treatment options targeting FRα. Developed and manufactured with Sutro’s cell-free XpressCF platform, luvelta is a homogeneous ADC with four hemiasterlin cytotoxins per antibody, precisely positioned to efficiently deliver to the tumor while ensuring systemic stability after dosing. REFRαME-O1, a Phase 2/3 registration-directed study for patients with platinum-resistant ovarian cancer is ongoing. The Company has additional ongoing trials in patients with endometrial cancer and in combination with bevacizumab in patients with ovarian cancer. The Company expects to file an Investigational New Drug (IND) Application for the initiation of a non-small cell lung cancer study in the first half of 2024 and expects to initiate REFRαME-P1, a Phase 2/3 registration-directed study for patients with CBF/GLIS2 acute myeloid leukemia, a rare subtype of pediatric cancer, in the second half of 2024. The U.S. Food and Drug Administration (FDA) has granted luvelta a Fast Track designation for Ovarian Cancer, as well as Orphan and Rare Pediatric Disease designations for CBF/GLIS2 Pediatric AML.