On August 14, 2018 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST), a clinical-stage biopharmaceutical company using its expertise in epigenetics to discover and develop novel therapeutics, reported its second-quarter and six-month 2018 financial results (Press release, Constellation Pharmaceuticals, AUG 14, 2018, View Source [SID1234528873]).

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"We at Constellation are pleased to report our financial results for the first time as a public company," said Jigar Raythatha, president and chief executive officer of Constellation Pharmaceuticals. "We are focusing our efforts and investing the capital that we raised in our recent crossover round and IPO with the goal of building a broad portfolio of important epigenetics-based medicines to serve inadequately treated cancer patients.

"We have many things to be excited about in the months ahead," Mr. Raythatha continued. "Our robust epigenetics platform has delivered multiple programs into the clinic that are testing differentiated approaches to treating cancer. These programs have provided encouraging preliminary clinical data, details of which we disclosed in our IPO prospectus. We look forward to providing further updates on the progress of our two lead programs in metastatic castration-resistant prostate cancer and myelofibrosis, including evaluation of proof of concept in mid-2019. We aim to expand on this clinical pipeline with new drug candidates generated by our epigenetics platform."

In conjunction with the Company’s IPO, Constellation is expanding its leadership team. To that end, in July the Company appointed Karen Valentine as Chief Legal Officer and General Counsel. "We are thrilled to have someone with Karen’s extensive legal and business experience in the biotech space join Constellation," Mr. Raythatha concluded. "We welcome her and will benefit considerably from her leadership."

News

On July 18, the Company priced its IPO of 4,000,000 shares at a price of $15.00 per share, for gross proceeds of $60 million, before underwriting discounts and commissions and offering expenses payable by the Company. On July 19, the Company’s common stock began trading on the Nasdaq Global Select Market under the symbol "CNST." The IPO closed on July 23.

On July 16, the Company appointed Karen Valentine as Chief Legal Officer and General Counsel. Ms. Valentine joins Constellation after serving as Chief Legal Officer and General Counsel of Agenus Inc.

In June, two scientific publications preclinically validated the role of the EZH2 inhibitor CPI-1205 in cancer immunotherapy. CPI-1205’s potential effect as an immunotherapy was first established through the Company’s collaboration with the laboratory of Dr. Padmanee Sharma at MD Anderson Cancer Center. The work is documented in "Modulation of EZH2 Expression in T Cells Improves Efficacy of anti-CTLA-4 Therapy," which was published in the Journal of Clinical Investigation. Constellation also contributed CPI-1205 product to a study by the laboratories of Dr. Jeffrey Bluestone at UCSF and Dr. Michel DuPage at UC Berkeley discussed in the article "Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity," published in Cell Reports. These studies support the rationale for the Company’s ORIOn-E trial.

On April 9, the Company announced completion of a $100 million financing, with funds provided by both existing and new investors. The Company plans to utilize the proceeds of this financing and of its IPO to advance its multiple clinical trials, including the ongoing ProSTAR and ORIOn-E trials for CPI-1205 and the ongoing MANIFEST trial for CPI-0610, to continue development of CPI-0209, and to advance its preclinical pipeline.

Second Quarter 2018 Financial Results

Cash and cash equivalents as of June 30, 2018 grew 24% to $88.5 million compared to March 31, 2018, primarily due to capital raised in a preferred stock offering in April, partially offset by operating expenses. This cash balance did not reflect proceeds from the IPO, which occurred in July.

Research and development (R&D) expenses increased 19% year over year to $9.5 million in the second quarter of 2018 mainly due to increased CPI-1205 clinical trial expenses.

General and administrative (G&A) expenses grew 67% year over year to $2.5 million in the second quarter of 2018, primarily due to increased personnel costs related to building out the organization as the Company evolves from a preclinical-stage company to a multi-candidate clinical-stage company, as well as costs associated with the IPO.

The net loss attributable to common stockholders decreased 3% year over year to $11.9 million and decreased 22% to $9.96 per share for the second quarter of 2018.

Financial Guidance

The Company expects that its cash and cash equivalents as of June 30, 2018, together with the proceeds of the IPO, will fund planned operations into the first quarter of 2020.

Overview of Key Programs

ProSTAR: CPI-1205 is a small molecule designed to promote anti-tumor activity by specifically inhibiting EZH2, an enzyme that suppresses target gene expression. The ProSTAR trial is an open-label Phase 1b/2 clinical trial of CPI-1205 in combination with either abiraterone acetate or enzalutamide, which are androgen receptor signaling (ARS) inhibitors, in patients with metastatic castration-resistant prostate cancer (mCRPC) who previously progressed on treatment with one of these ARS inhibitors. In the Phase 1b portion of this trial, the Company is aiming to establish safety, pharmacokinetics, pharmacodynamics, maximum tolerated dose and a recommended Phase 2 dose of CPI-1205 in combination with these agents. The Company has observed preliminary evidence of clinical activity in the Phase 1b portion of this trial. In the randomized Phase 2 portion, the Company will aim to assess the response rate of a selected combination of CPI-1205 and one of these ARS inhibitors compared to that of the ARS inhibitor alone.

ORIOn-E: In accordance with the Company’s franchise approach to targeting EZH2, the Company has initiated the ORIOn-E trial, a Phase 1b/2 clinical trial of CPI-1205 in combination with ipilimumab or pembrolizumab for the treatment of patients with solid tumors who have previously progressed on treatment with an immune checkpoint inhibitor that inhibits PD-L1 or PD-1. In the Phase 1b portion of the trial, the Company seeks to establish the safety, pharmacokinetics, maximum tolerated dose, and recommended Phase 2 dose of the combination.

MANIFEST: CPI-0610 is a potent and selective small molecule designed to promote anti-tumor activity by selectively inhibiting the function of BET proteins to decrease the expression of abnormally expressed genes in cancer. In MANIFEST, an open-label Phase 2 clinical trial, the Company is evaluating CPI-0610 as a second-line treatment for patients with myelofibrosis (MF), a progressive hematological cancer. The Company is studying CPI-0610 in combination with ongoing ruxolitinib treatment in MF patients who have experienced disease progression, and as a monotherapy in MF patients not eligible for, or no longer on, ruxolitinib. The Company aims to evaluate safety, pharmacokinetics, reduction in spleen volume, patient-reported symptom improvement and improvements in red-blood-cell transfusion independence rate in patients who were transfusion dependent at baseline.

CPI-0209: Also in accordance with our franchise approach to targeting EZH2, the Company has developed a second-generation EZH2 inhibitor, CPI-0209, and is currently conducting IND-enabling studies. The Company expects to provide additional updates on the development of CPI-0209 in the context of its EZH2 franchise approach in 2019.

In all of the above referenced clinical trials, the Company plans to collect and analyze biomarkers to assess the biology of the EZH2 or BET proteins, which may allow the Company to enrich for patients who are most likely to respond to treatment.

On August 14, 2018 Veru Inc. (NASDAQ: VERU), an oncology and urology biopharmaceutical company, reported its financial results for the fiscal 2018 third quarter ended June 30, 2018 (Press release, Veru, AUG 14, 2018, View Source [SID1234529157]).

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"We have made strong progress in this quarter advancing our pipeline of proprietary prostate cancer product candidates and suite of urology specialty pharmaceuticals," commented Mitchell Steiner, M.D., Chairman, President and Chief Executive Officer. "We look forward to enrolling the first patient in the Phase 2 trial of zuclomiphene (aka cis-clomiphene) to treat hot flashes caused by prostate cancer hormone therapy during the fiscal fourth quarter of 2018. Within this calendar year, we expect to conduct the bioequivalence studies for new formulation product candidates tamsulosin DRS granules and XR capsules, as well as tadalafil-finasteride combination tablets. Our product candidates address unmet medical needs in prostate cancer, prostate cancer supportive care, and urology which are multibillion dollar markets."

"With regard to our financial results: net revenues, which are primarily derived from product sales of FC2 Female Condoms, increased 28% in the third quarter of fiscal 2018 over the comparable prior year period and more than doubled from the preceding quarter. We are expecting the South African government to announce soon the results of the tender award for 40 million female condoms per year — a total of 120 million units over the full three-year tender time period — and we are confident that we will receive a substantial portion of the award."

Summary of Accomplishments During FY Q3

In June 2018, the Company submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration for a Phase 2 clinical study of zuclomiphene for the treatment of hot flashes in men with advanced prostate cancer who are receiving hormone therapy, which has been accepted. Also in June, the U.S. Patent and Trademark Office issued Patent No. 9,913,815, which provides protection until 2035 for the use of zuclomiphene in men with prostate cancer as a method of treating and preventing side effects caused by androgen deprivation therapy (ADT), including hot flashes, loss of bone mineral density and bone fractures.

In May 2018, preclinical results for VERU-111, a novel oral alpha and beta tubulin inhibitor with potential for development in the treatment of prostate and other cancer types, were featured in a moderated poster session at the 2018 American Urological Association Annual Meeting. In June 2018, preclinical results showing the efficacy of VERU-111 in four different cancer models (novel androgen blocking agent resistant human prostate cancer, a paclitaxel sensitive and resistant triple negative breast cancer, as well as ovarian cancer and pancreatic cancer) were presented as part of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.

Fiscal Third Quarter Results: 2018 vs. 2017

For the third quarter of fiscal 2018, net revenues increased to $5.5 million from $4.3 million for the third quarter of fiscal 2017. Gross profit rose to $3.1 million, or 56% of net revenues, from $2.3 million, or 53% of net revenues, for the third quarter of fiscal 2017. Operating expenses were $8.0 million compared with $3.6 million. Net loss was $7.9 million, or $0.15 per share, compared with $0.8 million, or $0.03 per share, for the third quarter of fiscal 2017.

Significant quarter-to-quarter variations in the Company’s results have historically resulted from the timing and shipment of large orders rather than from any fundamental changes in the business or the underlying demand for female condoms.

Conference Call Event Details

Veru Inc. will host a conference call on Tuesday, Aug. 14, 2018, at 8 a.m. Eastern Time to review the company’s performance. Interested investors may access the call by dialing 800-341-1602 from the U.S. or 412-902-6706 from outside the U.S. and asking to be joined into the Veru Inc. call.

In addition, investors may access a replay of the conference call the same day beginning at approximately noon ET by dialing 877-344-7529 for U.S. callers, or 412-317-0088 from outside the U.S., passcode 10122133. The replay will be available for one week, after which the recording will be available via the Company’s website at View Source

On August 13, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation (RPDD) to CLR 131, the company’s lead Phospholipid Drug Conjugate (PDC) product candidate, for the treatment of Ewing’s sarcoma, a rare pediatric cancer (Press release, Cellectar Biosciences, AUG 13, 2018, View Source [SID1234528817]).

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"We are delighted to announce receipt of our third RPDD from the FDA, which underscores Cellectar’s commitment to rare pediatric cancers. There is a critical need to develop new therapies to fight deadly childhood cancers such as Ewing’s sarcoma, and CLR 131 has shown early promise in this arena," said John Friend, M.D., chief medical officer of Cellectar Biosciences. "This designation, combined with our receipt of FDA Orphan Drug Designation for Ewing’s sarcoma last month, will help support our efforts to optimize the drug development path in this indication and, if successful, enable this new therapeutic candidate is made available to patients as rapidly as possible."

Since March 2018 the FDA has granted RPDDs to CLR 131 for the treatment of three separate rare disease indications including neuroblastoma, rhabdomyosarcoma and now Ewing’s sarcoma. Should CLR 131 be approved by the FDA in any of these indications, the RPDD may enable Cellectar to receive a priority review voucher. Priority review vouchers can be used by the sponsor to receive priority review designation for a future NDA or BLA submission, which could reduce the FDA review time from twelve months to eight months. Currently, these vouchers can also be transferred or sold to another entity. Since the beginning of 2017, six priority review vouchers were sold for between $80 million and $150 million each.

The FDA grants RPDD for diseases that primarily affect children from birth to age 18, and affect fewer than 200,000 persons in the U.S. This program is intended to encourage development of new drugs and biologics for the prevention and treatment of rare pediatric diseases.

Cellectar plans to evaluate CLR 131 in a Phase 1 clinical study for the treatment of pediatric patients with Ewing’s sarcoma, rhabdomyosarcoma, osteosarcoma, neuroblastoma, high-grade glioma and lymphomas. Cellectar has received clearance from the FDA for an accelerated Phase 1 trial designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of CLR 131 in pediatric patients with these cancer types. Further details about the trial can be found at clinicaltrials.gov using the identifier number NCT03478462.

About Ewing’s Sarcoma

Ewing’s sarcoma is the second most common bone malignancy among children and adolescents. According to a study published in the Journal of Hematology/Oncology, the incidence is about 3 cases per 1 million per year in children younger than age 20. Despite the favorable prognosis, an American Cancer Society study showed that approximately 30-40% of patients develop metastases or local recurrence, and the long-term survival rate for refractory or recurrent disease is only 22-24%. The relapsed and refractory statistics underscore the need for new treatment options.

About CLR 131

CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131, is in a Phase 2 clinical study in relapsed or refractory (R/R) MM and a range of B-cell malignancies and a Phase 1 clinical study in patients with (R/R) MM exploring fractionated dosing. The company is currently initiating a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma and is planning a second Phase 1 study in combination with external beam radiation for head and neck cancer.

On August 13, 2018 ArQule, Inc. (Nasdaq:ARQL), reported the publication of preclinical study data for ARQ 531, the Company’s rationally-designed, reversible inhibitor of both wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) (Press release, ArQule, AUG 13, 2018, View Source [SID1234532694]). The studies, published in Cancer Discovery, were conducted in collaboration with researchers at The Ohio State University. Data from these studies demonstrated efficacy in in vitro and in vivo hematologic malignancy models that recapitulate the most common mechanisms of resistance to irreversible BTK inhibitors, including ibrutinib.

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Highlights from the manuscript (link here) include:

Differentiated Crystal Structure and Biochemical Profile

The crystal structure of ARQ 531 bound to BTK elucidates the mechanism of BTK inhibition that is not dependent on the specific amino acid residue at position 481 (eg. C or S)
Recombinant BTK biochemical assays of ARQ 531 and ibrutinib show similar inhibition for wild type BTK, however ibrutinib has dramatically lower inhibition, binding affinity and residence time for mutant BTK
"Relapsed and refractory patients that develop resistance to ibrutinib have poor outcomes and limited treatment options," said Brian Schwartz, M.D., Chief Medical Officer and Head of R&D at ArQule. "ARQ 531 was rationally-designed and selected to address this unmet need by inhibiting both wild type and mutant BTK. The published crystal structure and biochemistry clearly demonstrate the mechanism by which ARQ 531 maintains binding and inhibition of mutant BTK in conditions where ibrutinib cannot."

Established Activity in Multiple Cellular and Murine Models of Hematological Malignancies

Exhibited dose dependent toxicity in human primary CLL cells (mutant and wild type)
Inhibited CLL cell migration in vitro
Established superiority to ibrutinib in an engraftment murine model of CLL
Showed activity against other B-cell signaling pathways
Demonstrated efficacy in a murine model of Richter’s transformation
John Byrd, M.D., the Warren Brown Chair of Leukemia Research at The Ohio State University stated, "The inhibition profile of ARQ 531 may confer distinct advantages over ibrutinib, potentially expanding the patient population beyond those with a C481S mutation who may benefit from treatment. Targeting multiple kinases in the B cell activation pathway may provide more durable responses to treatment while also delaying the emergence of treatment resistance. Jennifer Woyach, M.D., Associate Professor of Medicine at The Ohio State University, added, "I am particularly encouraged by the CLL mouse model data which established the superior efficacy of ARQ 531 compared to ibrutinib and the efficacy of ARQ 531 in the model of Richter’s transformation as this is an extremely aggressive disease with very few treatment options."

On August 13, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of cellular immunotherapies based on its novel, universal Antibody-Coupled T Cell Receptor (ACTR) technology platform, reported that an investigational new drug (IND) application is now active for ACTR T cells in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers (Press release, Unum Therapeutics, AUG 13, 2018, View Source [SID1234528936]). This represents the first solid tumor product candidate based on Unum’s novel, universal ACTR technology, and the fourth clinical trial program for the Company.

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"We are very happy to reach this important milestone for patients and for Unum," said Chuck Wilson, Chief Executive Officer of Unum. "ACTR represents a promising novel technology that can be used to target different tumor types and it’s exciting to expand its application to target solid tumors. We are committed to developing ACTR for patients with HER2+ advanced cancers who need better treatment options."

Under this IND, Unum is preparing to initiate a multi-center Phase I trial, called ATTCK-34-01, by the end of 2018 in patients with HER2+ advanced cancers. ATTCK-34-01 is designed as a dose escalation study where both the ACTR T cell drug product and trastuzumab doses are escalated in order to define the safety, tolerability, and anti-tumor activity of the combination. Expansion at the recommended Phase 2 dose is planned.