On August 6, 2019 Lixte Biotechnology Holdings, Inc. (OTCQB: LIXT) reported that it signed a clinical trial agreement with the Spanish Sarcoma Group (Grupo Español de Investigación en Sarcomas, GEIS) to support a Phase 1b/randomized Phase 2 study of doxorubicin, the global standard for initial treatment of advanced soft tissue sarcomas (ASTS), versus doxorubicin plus LB-100 (Press release, Lixte Biotechnology, AUG 6, 2019, View Source [SID1234538246]).

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Dr. John S. Kovach, CEO of Lixte, said, "We are pleased to support this investigator-initiated trial proposed by GEIS, a leader for many years in seeking improved therapies for ASTS. GEIS has a network of referral centers in Spain and across Europe that has an impressive track record of efficiently conducting innovative studies in ASTS. We believe GEIS and their EU collaborators are an excellent team to evaluate the potential benefit of adding Lixte’s non-cytotoxic inhibitor of DNA damage repair to standard treatment for this challenging disease. The goal is to enter the first patient in the last quarter of this year and to complete enrollment of approximately 170 patients over two years."

Dr. Kovach continued, "Doxorubicin alone has been the mainstay of first line treatment of ASTS for over 40 years with little therapeutic gain from adding cytotoxic compounds to or substituting other cytotoxic compounds for doxorubicin. In animal models, LB-100, an inhibitor of protein phosphatase2A (PP2A), consistently enhances the antitumor activity of doxorubicin without apparent increases in toxicity and, in a Phase 1 clinical trial, LB-100 alone was associated with stabilization of an advanced chondrosarcoma and fibrosarcoma for 6 and 9 months, respectively, without toxicity. LB-100 potentiates the effectiveness of agents like doxorubicin by inhibiting multiple steps required to repair chemotherapy induced DNA damage. We are excited to learn if the combination of LB-100 and doxorubicin will finally advance the effectiveness of ASTS therapy."

Dr. Javier Martin-Broto, Coordinating Investigator of the trial and medical oncologist at Virgen del Rocío University Hospital (Seville) commented, "Although there has been an increase in overall survival in advanced sarcoma in recent years, this gain has not been accompanied by advances in first line therapy. Anthracyclines, and specifically doxorubicin, is still the standard initial treatment. The growing list of negative phase III trials indicates to us that sarcoma therapy is in crisis. It is true that sarcoma encompasses more than 60 different subtypes and, for some of them, substantial advances have emerged. But it is also true that the most frequent sarcoma subtypes desperately need a turning point. One promising topic of research is the combination of doxorubicin with drugs that are able to impair the mechanisms of DNA repair. LB-100 has demonstrated synergistic action in in vivo preclinical mesenchymal tumors. GEIS will lead a European initiative to conduct a phase I/randomized II trial exploring the combination of doxorubicin plus LB-100 in first line of advanced soft tissue sarcomas".

On August 6, 2019 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer, autoimmune diseases, asthma and allergic diseases, reported financial results for the second quarter ended June 30, 2019 and provided a review of recent business and clinical highlights (Press release, Xencor, AUG 6, 2019, View Source [SID1234538188]).

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"Over the last two years, Xencor has initiated six Phase 1 clinical studies evaluating XmAb bispecific antibodies—both T cell engagers and tumor microenvironment (TME) activators—in patients with many types of advanced cancers, and we have also entered into strategic collaborations to advance select programs with our partners," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We anticipate several initial data presentations from these programs in the second half of 2019 and first half of 2020, and our strong financial position supports our broad pipeline and research into novel antibodies and cytokines engineered with XmAb bispecific technologies."

Dr. Dahiyat added, "In the second quarter, we reopened the Phase 1 study of XmAb14045 to enrollment, and patients have since begun treatment under the amended protocol. We also advanced our second and third TME activating bispecific antibodies into Phase 1 clinical studies. TME bispecific antibodies are designed with tuned dual checkpoint or checkpoint-agonist mechanisms to generate anti-tumor immune responses in a targeted manner. Finally, we continued to strengthen our senior leadership with appointments in business development and regulatory affairs."

Recent Business and Clinical Highlights and Anticipated Upcoming Milestones

CD3 Bispecific Antibodies: Xencor’s initial bispecific antibody programs are tumor-targeted antibodies that contain both a tumor antigen binding domain and a cytotoxic T-cell binding domain (CD3). These bispecific antibodies activate T cells for highly potent and targeted killing of malignant cells.

XmAb14045 (CD123 x CD3): Clinical sites participating in the Phase 1 study in patients with relapsed/refectory acute myeloid leukemia have resumed enrollment, and in early July the first patient was dosed under the study’s amended protocol. Amendments to the protocol included guidance on the monitoring and clinical management of cytokine release syndrome.
XmAb13676 (CD20 x CD3): A Phase 1 dose-escalation study began dosing patients with B-cell malignancies in February 2017. Enrollment in dose-escalation cohorts is ongoing, and initial data are expected in the fourth quarter of 2019.
XmAb18087 (SSTR2 x CD3): A Phase 1 dose-escalation study began dosing patients with neuroendocrine tumors or gastrointestinal stromal tumors in February 2018. Enrollment in dose-escalation cohorts is ongoing, and initial data are expected in the first half of 2020.
Tumor Microenvironment (TME) Activating Bispecific Antibodies: Xencor’s bispecific pipeline includes a suite of TME activators that engage multiple, different targets, such as T-cell checkpoint or agonist receptors. Xencor’s TME activators are designed to promote tumor-selective T-cell activation.

XmAb20717 (PD-1 x CTLA-4):A Phase 1 dose-escalation study in patients with advanced solid tumors began dosing patients in July 2018. Enrollment in dose-escalation cohorts is ongoing, and initial data are expected in the first half of 2020.
XmAb22841 (CTLA-4 x LAG-3): In May 2019, the first patient was dosed in a Phase 1 study evaluating XmAb22841 as a monotherapy and in combination with pembrolizumab in patients with select advanced solid tumors.
XmAb23104 (PD-1 x ICOS):In May 2019, the first patient was dosed in a Phase 1 study in patients with select advanced solid tumors.
Cytokines: Xencor uses its bispecific Fc domain and Xtend technology to engineer cytokines, which are immune signaling proteins, that have potency tuned to improve therapeutic index and have longer half-life.

XmAb24306 (IL15/IL15Rα-Fc fusion protein): The Company will support Genentech’s efforts to submit an IND application for this candidate, which is anticipated in the second half of 2019.
Partnered XmAb Programs: Xencor has eight licensing partnerships for XmAb technology. The most advanced program where the Company has licensed its technology is Alexion’s Ultomiris, which has received marketing authorizations for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) in the U.S. (December 2018), Japan (June 2019) and Europe (July 2019).

Corporate: In June 2019, Xencor announced the planned October 31, 2019 retirement of Paul Foster, M.D., Chief Medical Officer. As the Company searches for Dr. Foster’s successor, Xencor strengthened its senior management team in the second quarter with the appointments of Jeremy Grunstein, Ph.D., as vice president, business development, and Kirk Rosemark, as vice president, regulatory affairs and quality assurance.

Ultomiris is a registered trademark of Alexion Pharmaceuticals, Inc.

Second Quarter Ended June 30, 2019 Financial Results

Cash, cash equivalents and marketable securities totaled $626.1 million as of June 30, 2019, compared to $530.5 million at December 31, 2018. The increase reflects upfront proceeds of $135 million received in the first half of 2019 from the Genentech and Astellas collaborations, offset by cash used to fund operating activities in the first six months of 2019.

Total revenue for the second quarter ended June 30, 2019 was $19.5 million, which was primarily revenue recognized under the Astellas collaboration and a milestone and royalties earned from Alexion. Total revenue for the six months ended June 30, 2019 was $131.4 million and includes revenue earned from the Genentech and Astellas collaborations and the milestone and royalty revenue from Alexion. No revenue was reported for the same periods in 2018.

Research and development expenses for the second quarter of 2019 were $33.3 million, compared to $23.3 million for the same period in 2018. Total research and development expenses for the six months ended June 30, 2019 were $61.5 million, compared to $49.4 million for the same period in 2018. The increased research and development spending for the three and six months ended June 30, 2019 reflects increased stock-based compensation expense and additional spending on Xencor’s CD3 bispecific antibody and cytokine development candidates and technologies.

General and administrative expenses for the second quarter of 2019 were $5.8 million, compared to $5.0 million for the same period in 2018. Total general and administrative expenses for the six months ended June 30, 2019 were $11.3 million, compared to $9.5 million for the same period in 2018. The increased general and administrative spending for the three and six months ended June 30, 2019 reflects additional spending on intellectual property including patents and licensing and additional expenses related to personnel and professional services.

Non-cash, stock-based compensation expense for the six months ended June 30, 2019 was $15.2 million, compared to $9.4 million for the same period in 2018.

Net loss for the second quarter ended June 30, 2019 was $16.0 million, or $(0.28) on a fully diluted per share basis, compared to a net loss of $25.9 million, or $(0.46) on a fully diluted per share basis, for the same period in 2018. For the six months ended June 30, 2019, net income was $64.0 million, or $1.10 on a fully diluted per share basis, compared to a net loss of $55.4 million, or $(1.07) on a fully diluted per share basis, for the same period in 2018. The lower net loss reported for the three months ended June 30, 2019 over the same period in 2018 is primarily due to revenue from our Astellas and Alexion collaborations in 2019. The net income reported for the six months ended June 30, 2019 over the net loss reported for the same period in 2018 is primarily due to revenue recognized from our Genentech collaboration.

The total shares outstanding were 56,529,398 as of June 30, 2019, compared to 55,821,310 as of June 30, 2018.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations beyond 2024. Xencor expects to end 2019 with between $575 million and $600 million in cash, cash equivalents and marketable securities.

Conference Call and Webcast

Xencor will host a conference call today at 4:30 p.m. ET (1:30 p.m. PT) to discuss these second quarter 2019 financial results and provide a corporate update. The live call may be accessed by dialing (877) 359-9508 for domestic callers or (224) 357-2393 for international callers and referencing conference ID number 1597118. A live webcast of the conference call will be available under "Events & Presentations" in the Investors section of the Company’s website located at www.xencor.com. The webcast will be archived on the company website for 30 days.

On August 6, 2019 Vericel Corporation (NASDAQ:VCEL), a leader in advanced therapies for the sports medicine and severe burn care markets, reported financial results for the second quarter ended June 30, 2019, and recent business highlights (Press release, Vericel, AUG 6, 2019, View Source [SID1234538205]).

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Second Quarter 2019 Financial Highlights

Total net product revenues increased 38% to $26.2 million compared to $19.0 million in the second quarter of 2018;

Gross margin of 66% compared to gross margin of 59% in the second quarter of 2018;

Net loss of $19.8 million, or $0.45 per share, which includes the $17.5 million upfront license payment to MediWound for North American rights to NexoBrid;

Non-GAAP adjusted net loss, excluding the $17.5 million upfront license payment to MediWound, of $2.3 million, or $0.05 per share, compared to a net loss of $4.7 million, or $0.12 per share, in the second quarter of 2018;

Non-GAAP adjusted EBITDA of $1.8 million compared to a loss of $1.4 million in the second quarter of 2018;

As of June 30, 2019, the company had $66.0 million in cash and short-term investments compared to $82.9 million as of December 31, 2018; and

Full year 2019 revenue guidance for MACI and Epicel raised to $112 to $116 million compared to previous full year revenue guidance of $110 million to $114 million.

Recent Business Highlights
During and since the second quarter of 2019, the company:

Reported record second quarter revenues, marking the ninth consecutive quarter with record revenues for the reported quarter and the highest Epicel revenue for a second quarter in history;

Deployed the expanded MACI sales force, which increased from 40 to 48 sales representatives and initiated a MACI sales force sizing assessment based on an expanded target audience of approximately 5,000 surgeons who perform a high volume of cartilage repair procedures;

Announced an exclusive license agreement with MediWound for North American rights to NexoBrid, a registration-stage biological orphan product for debridement of severe thermal burns;

Announced that the U.S. Biomedical Advanced Research and Development Authority (BARDA) has agreed to fund the NexoBrid expanded access treatment (NEXT) protocol; and

Confirmed plans after meeting with the U.S. Food and Drug Administration (FDA) to submit a Biologics License Application (BLA) for NexoBrid to the FDA in the second quarter of 2020.

"The continued strength in MACI revenue growth reflects the increasing number of surgeons who view MACI as the standard of care for certain large, full thickness cartilage defects," said Nick Colangelo, president and CEO of Vericel. "Given the significant growth in new surgeons and biopsy volume, as well as the strength in Epicel demand, we have increased our revenue guidance for 2019. Looking forward, we anticipate submitting the NexoBrid BLA in the second quarter of 2020 which, upon FDA approval, would create a third growth driver for the company in 2021 and beyond."

Second Quarter 2019 Results
Total net product revenues for the quarter ended June 30, 2019 increased 38% to $26.2 million compared to $19.0 million in the second quarter of 2018. Total net product revenues for the quarter included $20.8 million of MACI (autologous cultured chondrocytes on porcine collagen membrane) net revenue and $5.3 million of Epicel (cultured epidermal autografts) net revenue, compared to $14.1 million of MACI net revenue and $4.9 million of Epicel net revenue, respectively, in the second quarter of 2018.

Gross profit for the quarter ended June 30, 2019 was $17.1 million, or 66% of net revenues, compared to $11.3 million, or 59% of net revenues, for the second quarter of 2018.

Total operating expenses for the quarter ended June 30, 2019 were $37.3 million, including the $17.5 million upfront license payment to MediWound Ltd. for North American Rights to NexoBrid. Excluding the $17.5 million license payment, operating expenses were $19.8 million, compared to $15.5 million for the same period in 2018. The increase in operating expenses was primarily due to a $1.4 million increase in stock-based compensation, an incremental $0.7 million in MACI sales force expenses as a result of the sales force expansion in 2019, and a $0.9 million increase in selling expenses and patient reimbursement support services.

Vericel’s net loss for the quarter ended June 30, 2019, which includes the $17.5 million upfront license payment for NexoBrid, was $19.8 million, or $0.45 per share. Non-GAAP adjusted net loss, excluding the $17.5 million upfront license payment for NexoBrid, was $2.3 million, or $0.05 per share, compared to a net loss of $4.7 million, or $0.12 per share, for the second quarter of 2018. See table reconciling non-GAAP measures for more details.Non-GAAP adjusted EBITDA was $1.8 million for the quarter ended June 30, 2019 compared to a loss of $1.4 million in the second quarter of 2018. See table reconciling non-GAAP measures for more details.
As of June 30, 2019, the company had $66.0 million in cash and short-term investments compared to $82.9 million as of December 31, 2018.

Full Year 2019 Financial Guidance
The company now expects total MACI and Epicel net product revenues for the full year 2019 to be in the range of $112 to $116 million, compared to the previous full year revenue guidance of $110 to $114 million.

Conference Call Information
Today’s conference call will be available live at 8:00am Eastern time in the Investor Relations section of the Vericel website at View Source." target="_blank" title="View Source." rel="nofollow">View Source A presentation supporting today’s conference call will be available on the webcast and in the Investor Relations section of the Vericel website. Please access the site at least 15 minutes prior to the scheduled start time in order to download the required audio software if necessary. To participate in the live call by telephone, please call (877) 312-5881 and reference Vericel Corporation’s second-quarter 2019 investor conference call. If calling from outside the U.S., please use the international phone number (253) 237-1173.

If you are unable to participate in the live call, the webcast will be available at View Source until August 6, 2020. A replay of the call will also be available until 11:00am (EDT) on August 11, 2019 by calling (855) 859-2056, or from outside the U.S. (404) 537-3406. The conference ID is 6576007.

On August 6, 2019 Cleave Therapeutics, Inc. (formerly Cleave Biosciences), a biopharmaceutical company focused on protein homeostasis and stress pathways in cancer and neurodegeneration, reported that it has appointed industry veterans Amy Burroughs as chief executive officer and Scott Harris as chief operating officer (Press release, Cleave Biosciences, AUG 6, 2019, View Source [SID1234538221]). Cleave also announced the closing of a $12 million financing to advance CB-5339, its second-generation, IND-ready, valosin-containing protein (VCP)/p97 inhibitor through early clinical development. The financing was led by 5AM Ventures, Celgene Corporation, Orbimed, U.S. Venture Partners (USVP), Arcus Ventures, Astellas Venture Management, and Osage University Partners (OUP).

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Cleave’s lead drug development candidate, CB-5339, is a potent, oral, selective, second-generation inhibitor of VCP/p97, which addresses limitations of earlier compounds, including exposure and selectivity to the target. The company is initiating a Phase 1 clinical study in acute myeloid leukemia (AML), for which there is compelling preclinical data and a significant unmet medical need. In addition, the National Cancer Institute, which has a decades-long interest in VCP/p97 as a target, is planning to sponsor a Phase 1 trial with CB-5339 in solid tumors in collaboration with Cleave.

"There is increasing scientific rationale supporting VCP/p97 as a key regulator of cell processes critical for cancer cell survival, particularly in acute myeloid leukemia (AML)," said Peter Thompson, MD, partner, Orbimed and Cleave co-founder. "The Cleave team has made significant progress in overcoming the challenges of earlier molecules, and generated robust preclinical data from strategic collaborators at the National Cancer Institute and academic institutions."

In addition to the management appointments, Laura Shawver, PhD, CEO of Synthorx, was named board chair of Cleave.

"We are thrilled that Cleave will be advancing CB-5339 to clinical development and welcome Ms. Burroughs to lead the company," said Dr. Shawver. "Amy has spent her career helping move novel drug candidates through the drug development process with a focus on understanding market needs, building partnerships and attracting top-notch talent. She will be instrumental as the company prepares for clinical studies in hematologic malignancies and solid tumors and continues to assess the potential in neurodegenerative diseases."

Ms. Burroughs brings more than 25 years of healthcare and life sciences leadership experience, most recently serving as executive-in-residence (EIR) at 5AM Ventures and as a strategic commercial advisor to Crinetics Pharmaceuticals. She began her biopharmaceutical career at Genentech and was previously founder and managing partner of The Ventral Group, a strategic life sciences consulting and investor advisory firm. Ms. Burroughs’ industry experience also includes consulting with Egon Zehnder and serving as the chief commercial officer and head of business development for APT Pharmaceuticals. She received her BA from Dartmouth College and her MBA from Harvard Business School, where she graduated as a Baker Scholar.

Scott Harris brings more than 20 years of broad cross-functional experience advancing novel products through preclinical and clinical development. Mr. Harris most recently held executive positions at two BridgeBio subsidiaries, including serving as executive vice president, corporate development and operations at Navire Pharma. Previously, he was executive vice president of regulatory affairs and technical operations at Adynxx, where he directed development activities from pre-clinical through Phase 2 studies. Mr. Harris also held positions of increasing responsibility at Corthera, BioMarin Pharmaceutical, Attenuon, Angstrom Pharmaceutical and Biosite. He obtained his BS in biochemistry and cell biology from University of California, San Diego, and his MS in regulatory affairs from San Diego State University.

About VCP/p97

VCP/p97 is a critical enzyme in the AAA (ATPases Associated with diverse cellular Activities) family of ATPases and is a key regulator of various aspects of protein homeostasis and cellular stress pathways that are critical for cancer cell growth and survival. Inhibition of VCP/p97 has been shown to impact multiple stress response pathways — including proteotoxic stress and DNA damage repair where cancer cells are differentially sensitive—and drive cancer cells past the tipping point towards apoptosis. In neurodegenerative diseases, VCP/p97 has been shown to be important for the health and function of mitochondria, and Cleave’s research has demonstrated the potential for therapeutic benefit for patients with these debilitating diseases.

On August 6, 2019 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ: MOR) reported its intention to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) based on its phase 2 L-MIND study of tafasitamab (MOR208) and lenalidomide in relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) (Press release, MorphoSys, AUG 6, 2019, View Source [SID1234538247]). A letter of intent was submitted to EMA in early July and MorphoSys plans to complete the MAA submission by mid-2020.

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L-MIND is a single-arm, open-label phase 2 study investigating the antibody tafasitamab in combination with lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma who are not eligible for high-dose chemotherapy and autologous stem cell transplantation. In July 2019, the company presented positive primary analysis data from L- MIND at the ICML conference in Lugano. These data will form the basis for the planned filing package of the MAA that, if granted, allows for earliest approval in Europe in 2021.

"We are excited about the progress we are making with our plan for a possible regulatory approval for tafasitamab in Europe," said Dr. Malte Peters, Chief Development Officer at MorphoSys. "The preceding constructive interaction with the European regulatory authorities has given us the confidence to pursue an MAA submission for approval in Europe based on L-MIND. This complements our current focus on seeking approval of tafasitamab in the U.S. on the basis of L-MIND, for which we will complete a BLA submission to the FDA by year-end."