On August 5, 2021 Galapagos NV (Euronext & NASDAQ: GLPG) reported its progress on earlier-stage programs as well as its commercial launch of filgotinib in Europe. Following recent setbacks, the company is moving forward with its revised strategy and operational restructuring announced in May (Press release, Galapagos, AUG 5, 2021, View Source [SID1234585857]). The unaudited H1 financial and operational results are further detailed in the H1 2021 report available on the website, www.glpg.com.

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"Multiple assets are moving through clinical development, and we recently reported positive topline data on our TYK2 compound GLPG3667. In a Phase 1b trial in psoriasis (Pso), clinical activity was observed at 4 weeks, combined with an encouraging safety and tolerability profile. We currently are running an extended dose escalation study in healthy volunteers, and plan to progress GLPG3667 to a Phase 2b dose finding study in Pso as well as a Phase 2 study in ulcerative colitis (UC) in 2022.

We continue to develop our SIK portfolio of molecules, and recently reported encouraging early data from the first patient studies with SIK2/3 inhibitor GLPG3970. In a Phase 1b trial in Pso (CALOSOMA), clinical activity was observed at 6 weeks, and in a Phase 2a trial in UC (SEA TURTLE), biologically important effects were observed on a number of objective endpoints, both of which point to the potential of SIK inhibition as a novel mode of action in inflammation. No activity was observed in the LADYBUG study in rheumatoid arthritis (RA). GLPG3970 was generally safe and well tolerated. Based on these encouraging data, we work on optimizing the pharmacology of follow-up compounds from our SIK portfolio, and plan to bring an improved SIK2/3 molecule into the clinic in 2022.

On the commercial side, we report rapid progress in establishing our commercial operations for Jyseleca across Europe, with 11 countries launched to date. Reimbursement procedures are on track, and we are on target to achieve our commercial objectives.

We remain excited about the potential of our target discovery platform, our drug development capabilities, and the strength of our teams. We want to thank our shareholders for their continued support and patience as we are working hard to build our pipeline and establish Galapagos as a fully integrated European biopharma," said Onno van de Stolpe, CEO of Galapagos.

Bart Filius, President and COO, added, "Following the strategic exercise announced at Q1, we are focused on advancing our pipeline, implementing our savings program, and diligently evaluating business development opportunities. At the same time, we have been delivering on the launch of Jyseleca, building out our organization in new European markets. In line with our review, we reiterate our 2021 operational cash burni guidance of between €580 million and €620 million. We believe that the decisions and actions taken put us on the strongest footing for the future. We look forward to a busy second half of the year, not the least of which is the expected outcome of the regulatory review in Europe of Jyseleca in UC."

(*) The 2020 comparatives have been restated to consider the impact of classifying the Fidelta business as discontinued operations in 2020.

Details of the financial results
Due to the sale of our fee-for-service business (Fidelta) to Selvita on 4 January 2021 for a total consideration of €37.1 million (including customary adjustments for net cash and working capital), the results of Fidelta are presented as "Net profit from discontinued operations" in our unaudited condensed consolidated income statements for the six months ended 30 June 2021 and 30 June 2020.

Revenues and other income from continuing operations
Our revenues and other income from continuing operations for the first six months of 2021 increased to €277.2 million compared to €217.2 million in the first six months of 2020. Our revenues from the Gilead collaboration in the first six months of 2021 (€253.2 million) related to (i) the exclusive access to our drug discovery platform (€115.7 million), (ii) the filgotinib revenue recognition (€136.1 million) and (iii) royalties (€1.4 million).

Our deferred income balance on 30 June 2021 includes €1.9 billion allocated to our drug discovery platform that is recognized linearly over 10 years, and €0.7 billion allocated for the filgotinib development (including considerations for the previous and the renegotiated collaboration combined) that is recognized over time until the end of the development period.

Results from continuing operations
We realized a net loss from continuing operations of €77.2 million for the first six months of 2021, compared to a net loss of €169.2 million for the first six months of 2020.

We reported an operating loss amounting to €97.6 million for the first six months of 2021, compared to an operating loss of €134.4 million for the same period last year.

Our R&D expenditure in the first six months of 2021 amounted to €268.8 million, compared to €262.9 million for the first six months of 2020. This increase, primarily related to our filgotinib program and our Toledo program, was compensated by a decrease for ziritaxestat, the osteoarthritis (OA) program with GLPG1972, and the program in atopic dermatitis (AtD) with MOR106. Personnel costs increased due to an increase in headcount compared to the same period last year and increased costs of our subscription right plans. This factor, and the increased cost of the commercial launch of filgotinib in Europe, contributed to the increase in our S&M and G&A expenses, which were respectively €29.1 million and €76.9 million in the first six months of 2021, compared to respectively €26.9 million and €61.8 million in the first six months of 2020.

We reported a non-cash fair value gain from the re-measurement of initial warrant B issued to Gilead, amounting to €2.8 million, mainly due to the decreased implied volatility of the Galapagos share price and its evolution between 31 December 2020 and 30 June 2021.

Net other financial income in the first six months of 2021 amounted to €17.1 million, compared to net other financial loss of €13.0 million for the first six months of 2020, which was primarily attributable to €33.4 million of currency exchange gain on our cash and cash equivalents and current financial investments in U.S. dollars, to €8.7 million of negative changes in (fair) value of current financial investments and financial assets and to €4.4 million of interest expenses. The other financial expenses also contained the effect of discounting our long term deferred income of €4.8 million.

Results from discontinued operations
The net profit from discontinued operations for the six months ended 30 June 2021 consisted of the gain on the sale of Fidelta, our fee-for-services business, for €22.2 million.

Group net results
We reported a group net loss for the first six months of 2021 of €55.0 million, compared to a group net loss of €165.6 million for the first six months of 2020.

Cash position
Current financial investments and cash and cash equivalents totaled €5,006.6 million on 30 June 2021, as compared to €5,169.3 million on 31 December 2020.

Total net decrease in cash and cash equivalents and current financial investments amounted to €162.7 million during the first six months of 2021, compared to a net decrease of €214.3 million during the first six months of 2020. This net decrease was composed of (i) €223.2 million of operational cash burn, (ii) offset by €2.6 million of cash proceeds from capital and share premium increase from exercise of subscription rights in the first six months of 2021, (iii) €5.8 million negative changes in (fair) value of current financial investments and €35.0 million of mainly positive exchange rate differences, (iv) €28.7 million cash in from disposal of subsidiaries, net of cash disposed.

Finally, our balance sheet on 30 June 2021 held a receivable from the French government (Crédit d’Impôt Rechercheiv) and a receivable from the Belgian Government for R&D incentives, for a total of both receivables of €142.7 million.

Outlook 2021
In 2021, we expect the European regulatory assessment of filgotinib for the treatment of UC and anticipate both an opinion from the Committee for Medicinal Products for Human Use (CHMP) and a decision from the European Commission later this year. We also expect additional reimbursement decisions for filgotinib in RA across a number of European countries. We are on track to complete the transition from our collaboration partner Gilead to us of the full European commercial operations for filgotinib by year-end, and we anticipate reporting on our own European sales of filgotinib starting in the second half of the year.

Completion of the recruitment in the global DIVERSITY Phase 3 trial with filgotinib in Crohn’s disease by our collaboration partner Gilead is also expected later this year.

With regard to our SIK portfolio, we are advancing our SIK3 inhibitor GLPG4399 in healthy volunteers this year, and we aim to advance a follow-up SIK2/3 preclinical candidate into the clinic in 2022.

Following the positive topline data from our TYK2 inhibitor, GLPG3667, we currently are running an extended dose escalation study in healthy volunteers, and we are preparing for a Phase 2b trial in Pso and a Phase 2 trial in UC next year.

In our other programs, by year-end we intend to finalize recruitment into the GLPG2737 Phase 2a trial in polycystic kidney disease.

Following the previously announced review of our plans for 2021, we reiterate our guidance for full year 2021 operational cash burn of €580 to €620 million.

First half-year report 2021

Galapagos’ financial report for the first half-year ended 30 June 2021, including details of the unaudited consolidated results, is accessible via www.glpg.com/financial-reports.

Conference call and webcast presentation

Galapagos will conduct a conference call open to the public tomorrow, 6 August 2021, at 14:00 CET / 8 AM ET, which will also be webcasted. To participate in the conference call, please call one of the following numbers ten minutes prior to commencement:

A question and answer session will follow the presentation of the results. Go to www.glpg.com to access the live audio webcast. The archived webcast will also be available for replay shortly after the close of the call.

On August 5, 2021 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported financial results for the second quarter ended June 30, 2021 and provided a corporate update (Press release, Arvinas, AUG 5, 2021, View Source [SID1234585856]).

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"Arvinas has made tremendous progress throughout the first half of 2021 and July, highlighted by our global collaboration with Pfizer to co-develop and potentially co-commercialize our estrogen receptor-targeting PROTAC degrader, ARV-471. This collaboration has the potential to be transformational, combining Arvinas’ leadership in targeted protein degradation with Pfizer’s global capabilities to enhance and potentially accelerate the development of ARV-471," said John Houston, Ph.D., President and Chief Executive Officer at Arvinas.

"Through the rest of the year, we look forward to advancing our entire pipeline of PROTAC targeted protein degraders and to several important data milestones, including interim data from the ARDENT Phase 2 trial of our androgen receptor-degrading PROTAC degrader, ARV-110, and Phase 1 dose escalation data from ARV-471 and ARV-110," continued Dr. Houston.

Business Highlights and Recent Developments

Announced a global collaboration with Pfizer to co-develop and co-commercialize ARV-471 for the treatment of patients with ER+ breast cancer. The deal includes an upfront payment to Arvinas of $650 million, a $350 million equity investment from Pfizer, and $1.4 billion in potential milestone payments. Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.
Initiated the first-in-human study of ARV-766, an androgen receptor (AR) degrader with a differentiated profile from ARV-110, in patients with metastatic castration-resistant prostate cancer.
Completed dose escalation in the Phase 1 study of ARV-471 for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.
Completed dose escalation in the Phase 1 study of ARV-110 for the treatment of metastatic castrate-resistant prostate cancer.
Anticipated Milestones and Expectations

ARV-471

Presentation of Phase 1 dose escalation trial data (at the San Antonio Breast Cancer Symposium, December 2021)
Initiation of a neoadjuvant study in early breast cancer (2H21)
Initiation of a combination trial of ARV-471 and everolimus in 2L/3L metastatic breast cancer (2H21)
ARV-110

Presentation of completed Phase 1 dose escalation data (2H21)
Presentation of interim data from the ARDENT Phase 2 dose expansion at 420 mg (2H21)
Initiation of combination trial with abiraterone (2H21)
Second Quarter Financial Results

Cash, Cash Equivalents, and Marketable Securities Position: As of June 30, 2021, cash, cash equivalents, and marketable securities were $605.1 million as compared with $688.5 million as of December 31, 2020. The cash, cash equivalents and marketable securities amounts do not reflect the global Pfizer collaboration agreement upfront payment of $650 million that was received in July 2021, or the equity investment by Pfizer of $350 million (which is subject to certain conditions including clearance under the Hart-Scott Rodino Antitrust Improvements Act of 1976, as amended). The decrease in cash, cash equivalents and marketable securities of $83.4 million for the first six months of 2021 was primarily related to net cash used in operating activities of $86.4 million (net of $4.0 million received from two collaborators), the purchase of lab equipment and lease-hold improvements of $1.5 million and net accretion of discounts/premiums and unrealized loss on marketable securities of $3.6 million, partially offset by cash provided from the exercise of stock options of $8.1 million.

Research and Development Expenses: Research and development expenses were $43.0 million for the quarter ended June 30, 2021, as compared with $23.4 million for the quarter ended June 30, 2020. The increase in research and development expenses of $19.6 million for the quarter was primarily related to increases in clinical trial and CMC expenses associated with our AR program of $7.3 million and our ER program of $3.4 million, in addition to increases in preclinical expenses of $8.9 million associated with exploratory programs and investments in platform research.

General and Administrative Expenses: General and administrative expenses were $14.4 million for the quarter ended June 30, 2021, as compared to $8.8 million for the quarter ended June 30, 2020. The increase of $5.6 million was primarily related to an increase in personnel costs, facility related costs and professional fees.

Revenue: Revenue was $5.5 million for the quarter ended June 30, 2021, as compared with $5.7 million for the quarter ended June 30, 2020. Revenue is generated from the license and rights to technology fees and research and development activities related to the collaboration and license agreement with Bayer that was initiated in July 2019, the collaboration and license agreement with Pfizer that was initiated in January 2018, and the amended and restated option, license and collaboration agreement with Genentech that was initiated in November 2017. The decrease of $0.2 million for the quarter was primarily related to a collaborator adding new targets in previous periods that extended the period of revenue recognition for that collaboration agreement.

Interest and Other Income: Interest and other Income was $1.6 million for the quarter ended June 30, 2021 as compared with $1.3 million for the quarter ended June 30, 2020. The increase of $0.3 million was primarily due to forgiveness of debt of $1.0 million, related to a State of Connecticut loan which was partially forgiven upon our satisfaction of certain jobs criteria, partially offset by lower interest income and lower refundable research and development credits from the State of Connecticut.

Net Loss: Net loss was $50.3 million for the quarter ended June 30, 2021, as compared with $25.2 million for the quarter ended June 30, 2020. The increase in net loss for the quarter was primarily due to increased research and development expenses and increased general and administrative expenses.

About ARV-110
ARV-110 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade the androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer.

ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies.

About ARV-471
ARV-471 is an investigational orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

In preclinical studies, ARV-471 demonstrated near-complete ER degradation in tumor cells, induced robust tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed superior anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of ARV-471; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.

About ARV-766
ARV-766 is an investigational orally bioavailable PROTAC protein degrader designed to selectively target and degrade androgen receptor (AR). In preclinical studies, ARV-766 degraded all resistance-driving point mutations of AR tested, including L702H, a mutation associated with treatment with abiraterone and other AR-pathway therapies.

ARV-766 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer. ARV-766 has demonstrated activity in preclinical models of resistance to currently available AR-targeted therapies.

On August 5, 2021 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the second quarter ended June 30, 2021 and provided a corporate update (Press release, Celldex Therapeutics, AUG 5, 2021, View Source [SID1234585855]).

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"Last month, Celldex reported positive data from our ongoing Phase 1b study of CDX-0159 in chronic inducible urticaria, where a single dose demonstrated a rapid, profound and durable response," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "These data not only spoke to the potential to bring patients suffering from urticaria an opportunity for fast, lasting and meaningful relief, but also showed that CDX-0159 safely depletes mast cells, a significant scientific and medical achievement that indicates CDX-0159’s potential to help other patients in need across a myriad of diseases with mast cell involvement."

Mr. Marucci continued, "Importantly, driven by these data, we successfully completed a $287.5 million follow-on offering which will support the expansion of the CDX-0159 program into later stage studies and additional indications, along with the continued development of our bispecific platform, which is exploring important pathways in inflammatory diseases, auto-immune disorders and oncology. We look forward to building on our successes in what promises to be an exciting second half of the year."

Recent Program Highlights

CDX-0159 – KIT Inhibitor Program

CDX-0159 is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

On July 9, Celldex reported interim data from the CDX-0159 single dose Phase 1b open label study, which were presented in a late-breaking poster discussion session as part of the European Academy of Allergy and Clinical Immunology (EAACI) Annual Congress 2021.

All 19 patients experienced a clinical response as assessed by provocation threshold testing; 18/19 (95%) experienced a complete response and 1/19 (5%) experienced a partial response.

Rapid onset of responses after dosing and sustained durability were observed and most patients with cold urticaria and symptomatic dermographism experienced a complete response by week 1 and by week 4, respectively. The median duration of response for patients was 77+ days (11+ weeks) for cold urticaria and 57+ days (8+ weeks) for symptomatic dermographism.

A single 3 mg/kg dose of CDX-0159 resulted in rapid, marked and durable suppression of serum tryptase and depletion of skin mast cells (87% depletion) as measured through biopsy. The kinetics of serum tryptase and skin mast cell depletion mirrored clinical activity which confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement.

CDX-0159 was generally well tolerated. The most common adverse events were hair color changes, mild infusion reactions, and transient changes in taste perception.

Celldex plans to present additional Phase 1b single dose data from the cold urticaria and symptomatic dermographism cohorts, including quality of life assessments, in the fall of 2021 and data from the cholinergic cohort in the first quarter of 2022.

Celldex continues to enroll patients in the Phase 1b multi-center randomized, double-blind, placebo-controlled study of CDX-0159 in chronic spontaneous urticaria (CSU). This study is designed to assess the safety of multiple ascending doses of CDX-0159 in up to 40 patients with CSU who remain symptomatic despite treatment with antihistamines. Treatment results from this study are planned for presentation at a scientific congress in early summer of 2022.

Celldex is expanding CDX-0159 development into prurigo nodularis, a chronic skin disease characterized by the development of hard, intensely itchy (pruritic) nodules on the skin. Of note, a patient with symptomatic dermographism enrolled in the chronic inducible urticaria study also had a diagnosis of prurigo nodularis. This patient experienced both a complete response of symptomatic dermographism and notable improvement of the prurigo nodularis symptoms on study. Initiation of this study is planned for the fourth quarter of 2021.

Manufacturing activities are also progressing as planned to support the introduction of the CDX-0159 subcutaneous formulation. Celldex plans to initiate a randomized, double-blind, placebo-controlled, Phase 1 study designed to evaluate the safety of single ascending doses of the subcutaneous formulation of CDX-0159 in healthy volunteers in the third quarter of 2021.
CDX-1140 – CD40 Agonist Program

CDX-1140 is a potent CD40 human agonist antibody developed by Celldex that the Company believes has the potential to successfully balance systemic doses for good tissue and tumor penetration with an acceptable safety profile.

In the Phase 1 study of CDX-1140 in patients with recurrent, locally advanced or metastatic solid tumors and B cell lymphomas, both the monotherapy and combination with CDX-301 portions of the trial are complete. Expansion cohorts are actively recruiting including CDX-1140 with KEYTRUDA (pembrolizumab) in patients with squamous cell head and neck cancer and non small cell lung cancer who have progressed on checkpoint therapy; and CDX-1140 with standard of care chemotherapy in first line metastatic pancreatic cancer. An update from this program is expected by end of 2021.
CDX-527 – Bispecific Antibody Program

CDX-527 is the first candidate developed by Celldex from its bispecific platform and utilizes the Company’s proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 co-stimulation with blockade of the PD-L1/PD-1 pathway.

In June, Celldex reported initial data from the Phase 1 dose-escalation study in up to ~40 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy to be followed by tumor-specific expansion cohorts, which were presented at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting. A good safety profile was observed along with promising pharmacodynamic and pharmacokinetic activity, which are important key hurdles for the development of bispecific antibodies. The study is designed to determine the MTD during a dose-escalation phase and to recommend a dose level for further study in the subsequent expansion phase. The expansion is designed to further evaluate the tolerability, and biologic and anti-tumor effects of selected dose level(s) of CDX-527 in specific tumor types. Enrollment to the dose escalation portion of the study has been completed and expansion cohorts are being planned; additional data is expected in 2022.
Corporate Highlights

In July, Celldex closed an underwritten public offering of common stock, including the full exercise of the underwriters’ option to purchase additional shares, for gross proceeds of $287.5 million. Celldex believes that the proceeds from this offering, together with current reserves, provide the cash runway to fund key clinical, regulatory and operational activities through 2025.
While Celldex’s clinical development programs have not been significantly, negatively impacted by COVID-19 to date, the Company continues to carefully monitor the evolving situation closely across all development programs and work to minimize potential impact/disruptions.

Second Quarter 2021 Financial Highlights and 2021 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of June 30, 2021 were $164.0 million compared to $176.1 million as of March 31, 2021. The decrease was primarily driven by second quarter cash used in operating activities of $11.9 million. At June 30, 2021, Celldex had 39.6 million shares outstanding. In July 2021, the Company issued 6,845,238 shares of its common stock in an underwritten public offering of common stock resulting in net proceeds to the Company of approximately $270.0 million, after deducting underwriting fees and offering expenses.

Revenues: Total revenue was $3.5 million in the second quarter of 2021 and $4.2 million for the six months ended June 30, 2021, compared to $0.2 million and $3.0 for the comparable periods in 2020. The increase in revenue was primarily due to an increase in services performed under our contract manufacturing and research and development agreements with Rockefeller University and Gilead Sciences, partially offset by a decrease in revenue from product development and licensing agreements as a result of the $1.8 million milestone payment received from Rockefeller University in the first quarter of 2020 related to Celldex’s manufacturing and development services agreement.

R&D Expenses: Research and development (R&D) expenses were $12.4 million in the second quarter of 2021 and $25.1 million for the six months ended June 30, 2021, compared to $9.7 million and $21.4 million for the comparable periods in 2020. The increase in R&D expenses was primarily due to an increase in clinical trial, contract research, and personnel expenses, partially offset by a decrease in rent expense.

G&A Expenses: General and administrative (G&A) expenses were $4.3 million in the second quarter of 2021 and $8.4 million for the six months ended June 30, 2021, compared to $3.5 million and $7.2 million for the comparable periods in 2020. The increase in G&A expenses was primarily due to higher personnel expenses.

Intangible Asset Impairment: The Company recorded a non-cash impairment charge of $3.5 million during the second quarter of 2020 due to the discontinuation of the CDX-3379 program.

Changes in Fair Value Remeasurement of Contingent Consideration: The loss on fair value remeasurement of contingent consideration was $0.3 million for the second quarter of 2021 and $0.7 million for the six months ended June 30, 2021, primarily due to changes in discount rates and the passage of time.

Net Loss: Net loss was $13.4 million, or ($0.34) per share, for the second quarter of 2021, and $29.9 million, or ($0.76) per share, for the six months ended June 30, 2021, compared to a net loss of $11.0 million, or ($0.50) per share, for the second quarter of 2020 and $23.7 million, or ($1.20) per share, for the six months ended June 30, 2020.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at June 30, 2021, along with the approximately $270.0 million in net proceeds raised in our July 2021 underwritten public offering of common stock, are sufficient to meet estimated working capital requirements and fund planned operations through 2025.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA.

On August 5, 2021 Cardiff Oncology, Inc. (Nasdaq: CRDF), a clinical-stage oncology company, developing new precision medicine treatment options for cancer patients in indications with the greatest unmet medical need including KRAS-mutated colorectal cancer, pancreatic cancer, and castrate-resistant prostate cancer, reported recent company highlights and financial results for the second quarter ended June 30, 2021 (Press release, Cardiff Oncology, AUG 5, 2021, View Source [SID1234585854]).

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"During the past few months, we have achieved important clinical milestones that have advanced our drug development programs and further highlighted the clinical benefits of onvansertib across indications representing some of the most difficult to treat cancers" said Mark Erlander, Ph.D., chief executive officer of Cardiff Oncology. "The added expertise in drug development, financial strategy and business development brought by our CMO, CFO and new board members comes at a pivotal time for the Company, as our strong cash position and recent progress in our clinical and preclinical programs has us poised for a steady cadence of catalysts over the coming months."

Dr. Erlander continued, "Our clinical progress during the second quarter was highlighted by advancements in our two KRAS-focused programs. In metastatic pancreatic ductal adenocarcinoma (mPDAC), where approximately 95% of patients have a KRAS mutation, we began dosing patients in our Phase 2 trial evaluating onvansertib in combination with nanoliposomal irinotecan, 5-FU and leucovorin. This trial is supported by the promising data from our lead KRAS-mutated metastatic colorectal cancer program presented in April, which showed that treatment with onvansertib plus irinotecan, 5-FU and bevacizumab resulted in an overall response rate and median progression free survival that compare favorably to historical controls. Looking forward, we expect continued progress in these and our castrate-resistant prostate cancer trial as well as advancements in our efforts to expand onvansertib’s pipeline of indications."

Program highlights for the quarter ended June 30, 2021, along with recent developments, include:

Corporate Highlights:

Strengthened company leadership with the appointments of Katherine L. Ruffner, M.D., as chief medical officer (CMO) and James E. Levine as chief financial officer (CFO)

Dr. Ruffner is a US-trained hematologist/oncologist with over 25 years of clinical care, oncology biotechnology and pharmaceutical drug development experience, most recently serving as vice president, clinical development for ALX Oncology. Mr. Levine joins Cardiff Oncology with over two decades of corporate and investment banking experience in the biotechnology and pharmaceutical sectors and was most recently the chief financial officer of Cidara Therapeutics.

Added two new independent members to the Board of Directors

Mani Mohindru, Ph.D., and Renee P. Tannenbaum, Pharm.D., were appointed as independent members of Cardiff Oncology’s Board of Directors in June 2021. Dr. Mohindru is an experienced biotech industry executive and is currently the chief executive officer of Novasenta, an early-stage biotechnology company, and a director on the Board of CytomX, Inc., a clinical-stage biopharmaceutical company. Dr. Tannenbaum currently serves as vice president of global partnering at Halozyme, Inc. and has in-depth expertise in business development and in establishing successful strategic partnerships.

Added as a member of FTSE Russell Indexes

As of the market open on June 28, 2021, Cardiff Oncology was included as a member of the small-cap Russell 2000 Index, the all-cap Russell 3000 Index, and the Russell Microcap Index.

KRAS-mutated Metastatic Colorectal Cancer (mCRC) Program:

Announced the upcoming presentation of new data from lead clinical program in KRAS-mutated mCRC on Wednesday, September 8, 2021

Updated data from the Phase 1b/2 trial evaluating onvansertib in combination with standard-of-care FOLFIRI/bevacizumab for the second-line treatment of patients with KRAS-mutated mCRC will be announced at a webinar on September 8, 2021 at 4:00 p.m. ET featuring the clinical trial principal investigator, Heinz-Josef Lenz, M.D., FACP (USC Norris Comprehensive Cancer Center), and key clinical advisor Afsaneh Barzi, M.D., Ph.D., (City of Hope Comprehensive Cancer Center). To register for the webinar, click here.

Announced updated data from the Phase 1b/2 trial evaluating onvansertib plus FOLFIRI/bevacizumab that continues to demonstrate robust response to treatment and progression-free survival in KRAS-mutated mCRC

The data were presented as part of a Key Opinion Leader webinar in April featuring Daniel H. Ahn, D.O., M.S. (Mayo Clinic Arizona), and Manish R. Sharma, M.D. (START Midwest), and showed robust patient response and progression-free survival when onvansertib is combined with standard-of-care therapy in second line KRAS-mutated mCRC. Data highlights from the Phase 1b trial, as of April 4, 2021, include:

7 of 18 (39%) evaluable patients achieved a partial response (PR)
Evaluable patients have a median progression free survival (mPFS) of 9.4 months (95% confidence interval: 7.85 months – not reached), more than double the historical 4.5-month mPFS from analysis of 23 randomized trials in second-line metastatic colorectal cancer (data from ~10,800 patients)¹
7 patients remain on treatment
Clinical responses were observed across different KRAS mutations, including the 3 most common in colorectal cancer (G12D, G12V, G13D)
The greatest decreases in plasma KRAS mutant allelic frequency (MAF) after 1 cycle of treatment were observed in patients achieving a PR
Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no major or unexpected toxicities attributed to onvansertib
Presented findings from the Expanded Access Program (EAP) for onvansertib in KRAS-mutated mCRC highlighting the clinical benefit of onvansertib in heavily pretreated patients

Findings from 20 evaluable EAP participants who were heavily pre-treated (median of 3 prior lines of treatment) were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 in April. Participants enrolled in the EAP had failed or progressed on multiple lines of standard-of-care treatment and were treated with the same combination regimen (onvansertib 15 mg/m2 + FOLFIRI/bevacizumab) and dosing schedule used in the ongoing Phase 1b/2 mCRC clinical trial. Highlights from the AACR (Free AACR Whitepaper) presentation included:

15 of 20 (75%) evaluable participants received an irinotecan-based regimen as their last therapy prior to enrolling in the EAP.
13 of 20 (65%) evaluable participants were progressing prior to enrolling in the EAP
Median progression free survival (mPFS) was 5.6 months (95% confidence interval: 2.7 months – not reached), which is significantly greater than historical controls (2-3 months)2
62.5% of participants had a greater than 50% decrease in KRAS MAF after one cycle of treatment and continue to show a durable response and have not reached mPFS
11 of 20 of evaluable participants remain on treatment
Onvansertib in combination with FOLFIRI/bevacizumab has been well tolerated with no serious adverse events (SAEs) reported
Metastatic Pancreatic Ductal Adenocarcinoma (mPDAC) Program:

Began dosing patients in the Phase 2 trial of onvansertib in metastatic PDAC

The trial is a key component of onvansertib’s KRAS-targeted clinical programs and is designed to assess the safety and preliminary efficacy of onvansertib in combination with nanoliposomal irinotecan (Onivyde), leucovorin and fluorouracil (5-FU) as a second-line treatment in patients with metastatic PDAC who have failed first-line gemcitabine-based therapy. The trial expects to enroll 40 patients at 6 U.S. sites. Onvansertib’s potential in mPDAC, where ~95% of patients have a KRAS mutation, is supported by the promising clinical data seen in KRAS-mutated mCRC patients treated with the combination of onvansertib, irinotecan and 5-FU (FOLFIRI).

Metastatic Castrate-Resistant Prostate Cancer (mCRPC) Program:

Identified an androgen-independent mechanism of synergy between onvansertib and abiraterone in mCRPC

Collaborative studies with the Massachusetts Institute of Technology featured in a virtual oral poster presentation at the AACR (Free AACR Whitepaper) Annual Meeting 2021 suggest that the androgen receptor signaling inhibitor abiraterone sensitizes certain prostate cancer cells to onvansertib via the induction of a mitosis related gene signature and disruption of mitotic spindle orientation. These results are consistent with previous findings showing that onvansertib and abiraterone synergize in an androgen receptor-independent manner in vitro and in vivo. Data from the studies also suggest that the identified mitosis related gene signature may be predictive of patient response to onvansertib-abiraterone combination therapy, a hypothesis that is being further assessed in the ongoing Phase 2 mCRPC trial.

Second Quarter 2021 Financial Results:

As of June 30, 2021, Cardiff Oncology had approximately $140 million in cash, cash equivalents and short-term investments.

Total operating expenses were approximately $7.0 million for the three months ended June 30, 2021, an increase of $2.9 million from $4.1 million for the same period in 2020. The increase in operating expenses is attributed to ongoing and new onvansertib clinical development programs and preclinical activities, additional outside services for legal fees mainly related to the expansion of our patent portfolio, recruiting fees and stock compensation expense.

Research and development expenses increased by approximately $1.6 million to $4.1 million for the three months ended June 30, 2021, from $2.5 million for the same period in 2020. The increase in research and development expenses was primarily due to advancing the onvansertib clinical and preclinical programs and recruitment fees to fill the critical position of chief medical officer.

Selling, general and administrative expenses increased by approximately $1.1 million to $2.8 million for the three months ended June 30, 2021, from $1.7 million for the same period in 2020. The increase is attributed to increased outside services for legal fees related to the expansion of our patent portfolio, recruitment fees, and stock compensation expense.

Net cash used in operating activities in the second quarter of 2021 was approximately $4.3 million, which is comparable to the $4.3 million for the same period in 2020.

On August 5, 2021 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor-infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported second quarter 2021 financial results and corporate updates (Press release, Iovance Biotherapeutics, AUG 5, 2021, View Source [SID1234585853]).

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Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "During the first half of 2021 we advanced our TIL pipeline and presented clinical data across multiple solid tumor indications and treatment settings, including single-agent TIL in metastatic non-small cell lung cancer and melanoma, as well as initial clinical data for TIL in combination with pembrolizumab in early line melanoma. Our top priority remains our ongoing work to address FDA feedback regarding the potency assays for lifileucel to support our planned BLA submission. We are increasingly confident in the broad potential for TIL as the next class of paradigm-shifting therapy for cancer patients with significant unmet need."

Second Quarter 2021 Highlights and Recent Corporate Updates

Regulatory

Potency assays for lifileucel: Following FDA feedback regarding the potency assays for lifileucel, Iovance will continue ongoing work developing and validating its potency assays and plans to submit additional assay data and anticipates meeting with the FDA before the end of 2021. The company’s biologics license application (BLA) submission for lifileucel is now expected to occur during the first half of 2022. Resolution of the potency assay for lifileucel in melanoma is also a key step towards our regulatory plans in other indications.
Clinical

TIL therapy in melanoma:
Metastatic melanoma: follow up data from Cohort 2 in the C-144-01 study of lifileucel in advanced melanoma were presented at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting. As of the April 2021 data cutoff for the presentation, the overall response rate (ORR) was 36.4% (4.5% complete response rate and 31.8% partial response rate) and median duration of response (DOR) was not reached at 33.1 months of median study follow up as assessed by investigators (n=66). Detailed Cohort 2 data were also published in a manuscript in the Journal of Clinical Oncology, an ASCO (Free ASCO Whitepaper) journal.
Anti-PD-1 naïve melanoma: initial clinical data for lifileucel in combination with pembrolizumab were presented in a poster at ASCO (Free ASCO Whitepaper) 2021. The ORR was 86% and the complete response rate was 43% at a median follow up of 8.2 months in anti-PD-1 naïve melanoma patients in Cohort 1A in the IOV-COM-202 basket study (n=7).
TIL therapy in non-small cell lung cancer (NSCLC):

LN-145 clinical data in metastatic NSCLC (mNSCLC): clinical data for LN-145 showed a 21.4% ORR and 64.3% disease control rate in mNSCLC patients from Cohort 3B in the IOV-COM-202 study (n=28), including two responders with PD-L1 negative tumors. All Cohort 3B patients had received one or more prior systemic therapies, including anti-PD-1 therapy, and all responders also received prior chemotherapy. Detailed results are anticipated at a medical meeting in 2021.
LN-145 in second-line mNSCLC: the first patient was dosed and more than 15 U.S. clinical sites have been activated in the registration-supporting IOV-LUN-202 study of LN-145 in patients with mNSCLC.
Research

Iovance is committed to advancing the next generation of TIL and related therapies and technologies. Late preclinical programs in IND-enabling studies include a novel IL-2 analog (IOV-3001) as well as a genetically modified TIL (IOV-4001). IOV-4001 leverages TALEN technology licensed from Cellectis S.A. to genetically knock out PD-1 in TIL cells.
Manufacturing

TIL manufacturing success: to date, nearly 500 patients have been dosed with Iovance TIL products with more than a 90 percent manufacturing success rate.
Iovance Cell Therapy Center (iCTC): the investigational new drug (IND) application amendment has been cleared and clinical manufacturing of TIL is expected to commence at the iCTC in the near future. Commercial manufacturing remains on track to commence with a potential regulatory approval.
Corporate

Cash position of $708.7 million on June 30, 2021 is expected to be sufficient well into 2023.
A strong organization of nearly 270 employees with an average of more than 3.5 years of cell therapy experience is in place to advance research, development, manufacturing, and commercial launch preparations.
Iovance continues to expand its intellectual property portfolio and currently owns more than 25 granted or allowed U.S. and international patents for compositions and methods of treatment in a broad range of cancers relating to the Gen 2 manufacturing process. Iovance’s Gen 2 patent rights are expected to provide exclusivity through 2038. Iovance’s portfolio also includes patent applications and granted patents directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic TIL modifications, tumor digest and fragment compositions and methods (including cryopreservation), and combinations of checkpoint inhibitors and TIL products.
Second Quarter and First Half 2021 Financial Results

Iovance held $708.7 million in cash, cash equivalents, investments and restricted cash at June 30, 2021 compared to $635.0 million at December 31, 2020. The cash position as of the second quarter is expected to be sufficient for more than two years based on the current operating plan.

Jean-Marc Bellemin, Chief Financial Officer, stated, "Our balance sheet remains strong to advance our operating plan, including launch preparations and pipeline development, with no immediate need to raise additional capital."

Net loss for the second quarter ended June 30, 2021, was $81.4 million, or $0.53 per share, compared to a net loss of $63.0 million, or $0.47 per share, for the second quarter ended June 30, 2020. Net loss for the six months ended June 30, 2020, was $156.8 million, or $1.04 per share, compared to a net loss of $132.6 million, or $1.02 per share, for the same period ended June 30, 2020.

Research and development expenses were $62.1 million for the second quarter ended June 30, 2021, an increase of $12.8 million compared to $49.3 million for the second quarter ended June 30, 2020. Research and development expenses were $118.1 million for the six months ended June 30, 2021, an increase of $11.8 million compared to $106.2 million for the same period ended June 30, 2020.

The increase in research and development expenses in the second quarter 2021 over the prior year period was primarily attributable to an increase in costs associated with growth of the internal research and development team and increases in manufacturing and iCTC facility related costs. The increase in research and development expenses in the first half of 2021 over the prior year period was primarily attributable to growth of the internal research and development team, an increase in iCTC facility related costs, which were partially offset by lower manufacturing and clinical costs following the completion of enrollment in the pivotal cohorts for melanoma and cervical cancer.

General and administrative expenses were $19.3 million for the second quarter ended June 30, 2021, an increase of $5.0 million compared to $14.4 million for the second quarter ended June 30, 2020. General and administrative expenses were $38.9 million for the six months ended June 30, 2021, an increase of $10.7 million compared to $28.2 million for the same period ended June 30, 2020.

The increases in general and administrative expenses in the second quarter and first half of 2021 compared to the prior year periods were primarily attributable to growth of the internal general and administrative team and higher stock-based compensation expenses.

Webcast and Conference Call

Iovance will host a conference call today at 4:30 p.m. ET to discuss the second quarter 2021 financial results and corporate updates. The conference call dial-in numbers are 1-(844) 646-4465 (domestic) or 1-(615) 247-0257 (international) and the access code is 1489438. The live webcast can be accessed in the Investors section of the company’s website at View Source The archived webcast will be available for a year in the Investors section at www.iovance.com.