On August 11, 2021 Diffusion Pharmaceuticals Inc. (NASDAQ: DFFN) ("Diffusion" or the "Company"), an innovative biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen to areas where it is needed most, reported financial results for the second quarter of 2021 and provided a business update (Press release, Diffusion Pharmaceuticals, AUG 11, 2021, View Source [SID1234587026]).

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"We met our key milestones for the first half of 2021, completing and announcing topline results from our COVID-19 Trial and the first of our Oxygenation Trials. Our development plan remains on track. With the positive outcomes of the COVID-19 and TCOM studies, as well as our significant capital raise in the first quarter, we believe we have the data and the financial capacity to execute our clinical development strategy for TSC through Phase 2b. For the remainder of 2021, we are focused on the design and execution of the remaining two Oxygenation Trials to further our understanding of TSC’s mechanism of action and potential, as well as the further development of our regulatory and commercial strategy for TSC," said Robert Cobuzzi, Jr. Ph.D., President and CEO of Diffusion.

TSC Q2 Development Update

In May 2021, Diffusion reported final results from its Phase 1b trial (the "COVID-19 Trial") of trans sodium crocetinate ("TSC") in hospitalized COVID-19 patients. Although the study was not designed or powered to evaluate efficacy, the study’s external safety monitoring committee observed that patients receiving the 1.5 mg/kg dose of TSC had improved outcomes in secondary and exploratory endpoints compared to those receiving lower doses. The final results were consistent with topline results previously announced in February 2021, indicating that TSC was safe and well-tolerated when administered on a more frequent dosing regimen than previously tested in a clinical trial setting.

In June 2021, the Company reported a positive trend in oxygenation from its Phase 1b trial (the "TCOM Trial") evaluating TSC using transcutaneous oxygen monitoring ("TCOM"). The TCOM Trial was designed to evaluate the effect of TSC versus placebo on peripheral tissue oxygenation in healthy normal volunteers. Topline results based upon analyses of primary endpoint data indicated, as compared to placebo, a positive dose-response trend in TCOM readings after TSC administration that persisted through the measurement period with no evidence of hyperoxygenation. TSC was also safe and well-tolerated at all doses tested.

TSC Development Plans for 2021 and 2022

The positive trend observed in the TCOM Trial is being used to guide dose selection in the additional Oxygenation Trials planned for the latter part of 2021 – the Altitude Trial, followed by the ILD-DLCO Trial.

Altitude Trial (formerly known as the Induced Hypoxia Trial): This trial will be a double-blind, randomized, placebo-controlled study which will evaluate the effects of TSC on maximal oxygen consumption, or VO2, and partial pressure of blood oxygen, or PaO2, in normal healthy volunteers subjected to incremental levels of physical exertion while exposed to hypoxic and hypobaric conditions (i.e., simulated altitude). The study is designed to evaluate the effect of TSC versus placebo on maximal oxygen consumption and partial pressure of blood oxygen. Diffusion anticipates initiating and completing the Altitude Trial in the fourth quarter of 2021, with topline results available within one to two months of study completion.

ILD – DLCO Trial: This trial will be a double-blind, randomized, placebo-controlled study which will evaluate the effects of TSC on the diffusion of carbon monoxide through the lungs ("DLCO") in patients with previously diagnosed interstitial lung disease ("ILD") who have a baseline DLCO test result that is abnormal. DLCO will act as a surrogate measure of oxygen transfer efficiency, or uptake, from the alveoli of the lungs, through the plasma, and onto hemoglobin within red blood cells. The study will be statistically powered to evaluate the difference in effect of TSC versus placebo on improvement in DLCO as well as in a standard six-minute walk test. Diffusion now anticipates initiating the ILD-DLCO Trial in the late fourth quarter of 2021 and completing the trial in the first quarter of 2022, with topline results available within one to two months of study completion.

Diffusion expects to announce in the fourth quarter of 2021 the initial indication in which TSC will be studied to support the planned pathway for regulatory approval and to initiate a controlled, clinical outcome study evaluating TSC in the chosen indication during the first half of 2022, funded with cash-on-hand.

Operating and Leadership Team Developments

During the second quarter, Diffusion enhanced its operating team with the addition of new employees in the areas of administration, quality assurance, clinical operations, and finance. In addition, in connection with the Diffusion’s annual meeting of stockholders in June 2021, Jane H. Hollingsworth was elected as the new chair of the Company’s board of directors and Diana Lanchoney, M.D. and Eric Francois were newly elected to the board of directors. The Company believes these organizational additions have already had a significant, positive impact on its ability to develop, implement and execute on its corporate strategy and development plans, and position the Company well to build shareholder value through its next stage of growth.

2Q21 Financial Results

Research and development expenses in the second quarter were $2.0 million compared to expenses of $2.2 million in the prior year period. The decrease was attributable to the wind-down of the Company’s clinical trial evaluating TSC in glioblastoma multiforme brain cancer and its COVID-19 Trial completed in February 2021. These decreases were offset by increased headcount and costs related to the TCOM Trial.

General and administrative expenses were $1.8 million during the second quarter of 2021 versus $1.5 million in the comparable quarter last year. The increase compared to the prior year period was primarily attributable to increased salaries, wages, stock-based compensation, and professional fees related to increased headcount and costs associated with the separation of former employees that will not recur in future years.

As of June 30, 2021, Diffusion had cash and cash equivalents of approximately $43.3 million as compared to $18.5 million as of December 31, 2020.

On August 11, 2021 Terumo Blood and Cell Technologies (Terumo), a medical device company specializing in a portfolio of technology, software and services for blood component collection, therapeutic apheresis and cellular technologies, and PhotonPharma Inc., a cancer immunotherapy developer, reported they have established a memorandum of understanding (MOU) for collaboration to develop Innocell, a novel tumor specific immunotherapy (a therapeutic vaccine) for solid tumors (Press release, PhotonPharma, AUG 11, 2021, View Source [SID1234586670]). The benefit to patients is that collaborations like this can help improve the speed to market for valuable treatments.

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T-cell attaching to cancer cell, illustration T lymphocyte (orange) attached to a cancer cell (blue), illustration. T lymphocytes are a type of white blood cell which matures in the thymus. Certain kinds of T lymphocytes can recognise specific sites (antigens) on the surface of cancer cells or pathogens and bind to them. They can then destroy the cancer cells, or signal for other immune system cells to eliminate them. The genetic changes that cause a cell to become cancerous lead to the present
T-cell attaching to cancer cell, illustration T lymphocyte (orange) attached to a cancer cell (blue), illustration. T lymphocytes are a type of white blood cell which matures in the thymus. Certain kinds of T lymphocytes can recognise specific sites (antigens) on the surface of cancer cells or pathogens and bind to them. They can then destroy the cancer cells, or signal for other immune system cells to eliminate them. The genetic changes that cause a cell to become cancerous lead to the present
To help in the caner immunotherapy development process, PhotonPharma is using Terumo’s Mirasol Pathogen Reduction Technology (PRT) in the manufacturing process. The initial agreement authorizes PhotonPharma to reference the Device Master File (DMF) on record with the FDA for the Mirasol system. This DMF will then support the PhotonPharma regulatory submission for its Innocell therapeutic vaccine technology. Additionally, Terumo Blood and Cell Technologies will supply Mirasol illuminators and single-use sets for the immunotherapy preparation process used in the clinical trial.

Mirasol has been used in select markets outside the United States since 2007. Terumo designed Mirasol to reduce pathogen load and inactivate residual white blood cells in whole blood and blood components. PhotonPharma’s specific use of Mirasol is a further example of how Terumo’s products are being used to develop treatments across the life-sciences sector to help patients gain access to medical therapies.

Another potential therapy in the War Against Cancer
The American Cancer Society’s 2021 forecast projects 1.9 million new cancer diagnoses and more than 600,000 cancer deaths. Each day, that’s approximately 5,200 newly diagnosed cancer cases and 1,670 cancer deaths. Ninety percent of the cases diagnosed are expected to be from solid tumors2.

Therapeutic cancer vaccines are developed to stimulate a patient’s immune system to fight an established cancer. They are different from prophylactic vaccines, which are given to healthy individuals to prevent an infection and related disease.

PhotonPharma developed its technology to be differentiated from other therapeutic cancer vaccines in its potential to preserve solid tumor antigens, cell metabolism and protein translation while also potentially achieving inactivation of cellular replication.

This MOU is the first part of a longer-term collaboration to advance PhotonPharma’s Innocell. The collaboration focuses on the development, regulatory approval and future commercialization of PhotonPharma’s Innocell vaccine. PhotonPharma is currently preparing an Investigational New Drug (IND) submission related to a phase I clinical trial targeting triple-negative breast cancer.

"This agreement to work together with Terumo increases the potential to advance a new therapy for patients suffering from a variety of solid tumor malignancies including breast cancer," said Dr. Gary Gordon, M.D., Ph.D., former Divisional Vice President of Abbvie Oncology and PhotonPharma board member. "Working together will benefit patients in need of new therapeutic approaches to treat their underlying disease."

Antoinette Gawin, President and Chief Executive Officer, Terumo Blood and Cell Technologies, says: "For Terumo, strategic collaborations increase the potential speed to market and decrease development costs of therapies. This will enable patients to benefit from therapies earlier. Contributing toward the development and commercialization of Innocell enables Terumo to contribute toward the next potential major medical breakthrough."

1American Cancer Society. (2021). Retrieved 4 August 2021 from Cancer.org.

On August 11, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported the U.S. Food and Drug Administration (FDA) granted a sixth regulatory designation to lead drug candidate, repotrectinib (Press release, Turning Point Therapeutics, AUG 11, 2021, View Source [SID1234586469]).

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The Fast-Track designation was granted for the treatment of patients with ROS1-positive advanced non-small cell lung cancer (NSCLC) who have been previously treated with one prior ROS1 tyrosine kinase inhibitor (TKI) and who have not received prior platinum-based chemotherapy.

"We are pleased to receive our fourth Fast-Track designation and sixth overall regulatory designation for repotrectinib as we continue to work toward our goal of getting this ROS1 targeted therapy to patients quickly," said Athena Countouriotis, M.D., president and chief executive officer. "We continue to believe repotrectinib has the potential to be a best-in-class treatment for patients with ROS1-positive advanced non-small cell lung cancer or NTRK-positive advanced solid tumors and now have multiple regulatory designations in both the TKI-naïve and TKI-pretreated ROS1 patient populations."

Repotrectinib was previously granted Breakthrough Therapy designation in ROS1- positive metastatic NSCLC patients who have not been treated with a ROS1 tyrosine kinase inhibitor, as well as three Fast-Track designations in ROS1-positive advanced NSCLC patients who are ROS1 TKI naïve, ROS1-positive advanced NSCLC patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior ROS1 TKI, and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have no satisfactory alternative treatments.

About Fast-Track Designation
Fast-Track is an FDA program intended to facilitate the development and expedite the review of drug candidates to treat serious conditions and fill an unmet medical need.

A drug candidate that receives Fast-Track designation may be eligible for:

More frequent meetings with the FDA to discuss the drug’s development plan and ensure collection of appropriate data needed to support drug approval;
More frequent written communication with the FDA;
Eligibility for Accelerated Approval and Priority Review, if relevant criteria are met; and
Rolling submission of a New Drug Application (NDA) for review by FDA.

On August 11, 2021, ImmunoGen, Inc. (the "Company") reported that entered into a Securities Purchase Agreement (the "Securities Purchase Agreement") with RA Capital Healthcare Fund, L.P. (the "Investor"), pursuant to which the Company agreed to sell to the Investor a pre-funded warrant (the "Pre-Funded Warrant") to purchase up to an aggregate of 5,434,782 shares of the Company’s common stock, par value $0.01 per share ("Common Stock"), for aggregate consideration of $29,945,648.82, or $5.51 per share of Common Stock underlying the Pre-Funded Warrant, which, together with the per share exercise price, is equal to $5.52, the closing price of our Common Stock as reported on the Nasdaq Global Select Market on August 4, 2021, the date the Company and the Investor first discussed a potential investment (Filing, 8-K, ImmunoGen, AUG 11, 2021, View Source [SID1234586420]).

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The issuance and sale of the Pre-Funded Warrant under the Securities Purchase Agreement (and the shares of Common Stock issuable upon exercise of the Pre-Funded Warrant) are registered pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-251502).

The Securities Purchase Agreement contains certain representations, warranties, and covenants for the benefit of the parties to the Securities Purchase Agreement and should not be relied upon by any of our investors who are not parties to Securities Purchase Agreement, nor should any such investor rely upon any descriptions thereof as characterizations of the actual state of facts or condition. Such investors are not third-party beneficiaries under the Securities Purchase Agreement.

Pre-Funded Warrant

Pursuant to the Securities Purchase Agreement, the Company will issue the Pre-Funded Warrant to the Investor. The Pre-Funded Warrant entitles the Investor to purchase shares of Common Stock at an exercise price equal to $0.01 per share. The Pre-Funded Warrant will be exercisable at any time beginning on the date of issuance. The number of shares of the Company’s Common Stock issuable upon exercise of the Pre-Funded Warrant is subject to adjustment upon certain corporate events, including certain stock dividends and splits, combinations, reclassifications, and certain other events.

The Investor may exercise the Pre-Funded Warrant by delivering an exercise notice, completed and duly signed, and payment in cash of the exercise price for the number of shares of the Company’s Common Stock for which the Pre-Funded Warrant is being exercised. The Investor may also satisfy its obligation to pay the exercise price through a "cashless exercise," in which the Investor receives the net value of the Pre-Funded Warrant in shares of Common Stock determined according to the formula set forth in the Pre-Funded Warrant.

The Investor will not be entitled to exercise any portion of the Pre-Funded Warrant that, upon giving effect to such exercise, would cause the aggregate number of shares of Common Stock beneficially owned by the Investor (together with its affiliates and any other persons whose beneficial ownership of Common Stock would be aggregated with the Investor for purposes of Section 13(d) of the Securities Exchange Act of 1934, as amended) to exceed 9.99% of the total number of then issued and outstanding shares of Common Stock, as such percentage ownership is determined in accordance with the terms of the Pre-Funded Warrant. This threshold is subject to the Investor’s rights under the Pre-Funded Warrant to increase or decrease such percentage to any other percentage not in excess of 19.99% upon at least 61 days’ prior notice from the Investor to the Company.

On August 11, 2021 TRACON Pharmaceuticals (NASDAQ:TCON), a clinical stage biopharmaceutical company focused on the development and commercialization of novel targeted cancer therapeutics and utilizing a cost efficient, CRO-independent product development platform to partner with ex-U.S. companies to develop and commercialize innovative products in the U.S., reported financial results for the second quarter ended June 30, 2021 (Press release, Tracon Pharmaceuticals, AUG 11, 2021, View Source [SID1234586371]). The Company will host a conference call and webcast today at 4:30 PM Eastern Time / 1:30 PM Pacific Time.

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"We remain on track to announce interim efficacy data from the pivotal ENVASARC trial by the end of this year and final data in 2022," said Charles Theuer, M.D., Ph.D., President and CEO of TRACON. "Last week the IDMC recommended the study proceed as planned following review of interim safety data and we will continue to focus our efforts on enrolling this pivotal trial. Following our recent public offering, our balance sheet provides us with cash runway into 2023."

Recent Corporate Highlights

Envafolimab

In June, we received orphan drug designation for envafolimab in soft tissue sarcoma based on clinical data demonstrating confirmed objective partial responses by RECIST with duration of response in excess of six months, in two of five patients with refractory metastatic alveolar soft part sarcoma (ASPS) who received single agent envafolimab in Phase 1 clinical trials conducted by our partners, 3D Medicines and Alphamab Oncology.

On August 6, the Independent Data Monitoring Committee (IDMC) recommended the ENVASARC trial proceed as planned following the review of more than three months of safety data from more than 20 patients enrolled in the trial as of May.

In June, we presented the study design of the pivotal Phase 2 ENVASARC trial of single agent envafolimab and envafolimab given with Yervoy (ipilimumab) at the 2021 ASCO (Free ASCO Whitepaper) virtual annual meeting.
Corporate

In July, we announced an underwritten public offering for gross proceeds of approximately $15.0 million. We estimate that the proceeds will extend our cash runway into 2023, past expected final top-line data for ENVASARC.

In the second quarter we enhanced our senior management team with multiple new hires, including a Head of Regulatory and Head of Biometrics, both of whom have BLA filing experience.

In July, the book Unnecessary Expense: An Antidote to the Billion Dollar Drug Problem, authored by TRACON senior management to be published by ForbesBooks became available for preorder on Amazon. Publication is expected in September.
Other

In June, we presented preliminary Phase 1 data for the CD73 antibody uliledlimab (TJ4309) at the 2021 ASCO (Free ASCO Whitepaper) virtual annual meeting.
Expected Key Upcoming Milestones

Interim ENVASARC efficacy data by end of 2021.

Request FDA breakthrough therapy designation or fast track designation for envafolimab by end of 2021, assuming positive interim efficacy data.

Decision on the envafolimab New Drug Application in MSI-H/dMMR cancer that is under priority review by the Chinese National Medical Products Administration.
Second Quarter 2021 Financial Results

Cash, cash equivalents and short-term investments were $25.6 million at June 30, 2021, compared to $36.1 million at December 31, 2020. The cash balance at June 30, 2021, does not include the proceeds from the $15 million underwritten public offering in July, which extends the Company’s cash runway into 2023.

Research and development expenses for the second quarter of 2021 were $3.1 million, compared to $2.2 million for the second quarter of 2020.

General and administrative expenses for the second quarter of 2021 were $6.1 million, compared to $2.1 million for the second quarter of 2020. The increase was primarily attributable to legal expenses incurred with the now stayed lawsuit filed by I-Mab in the Delaware Court of Chancery and ongoing arbitration on the TJ4309 and bispecific agreements. We expect the second quarter of 2021 to be the high point for general and administrative expenses this year.

Net loss for the second quarter of 2021 was $8.9 million, compared to $4.5 million for the second quarter of 2020.
Conference Call Details

Wednesday, August 11, at 4:30 PM Eastern Time / 1:30 PM Pacific Time
Domestic: 855-779-9066
International: 631-485-4859
Conference ID: 3067769
A live webcast of the conference call will be available online from the Investor/Events and Presentations page of the Company’s website at www.traconpharma.com.

After the live webcast, a replay will remain available on TRACON’s website for 60 days.

About Envafolimab

Envafolimab (KN035), a novel, single-domain antibody against PD-L1, is the first subcutaneously injected PD-(L)1 inhibitor to be studied in pivotal trials. Envafolimab is currently being studied in the ENVASARC Phase 2 pivotal trial in the U.S. sponsored by TRACON, has been studied in a completed Phase 2 pivotal trial as a single agent in MSI-H/dMMR advanced solid tumor patients in China and is being studied in an ongoing Phase 3 pivotal trial in combination with gemcitabine and oxaliplatin in advanced biliary tract cancer patients in China, with both Chinese trials sponsored by 3D Medicines. TRACON’s partners Alphamab Oncology and 3D Medicines submitted an NDA to the NMPA in China for envafolimab in MSI-H/dMMR cancer that was accepted for review in December 2020 and granted priority review in January 2021. In the Phase 2 MSI-H/dMMR advanced solid tumor trial, the confirmed objective response rate (ORR) by blinded independent central review in MSI-H/dMMR colorectal cancer (CRC) patients treated with envafolimab who failed a fluoropyrimidine, oxaliplatin and irinotecan was 32%, which was similar to the 28% confirmed ORR reported in the Opdivo package insert in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin, and irinotecan and the 33% confirmed ORR reported for Keytruda in MSI-H/dMMR CRC patients who failed a fluoropyrimidine, oxaliplatin and irinotecan in cohort A of the KEYNOTE-164 clinical trial.

About ENVASARC (NCT04480502)

The ENVASARC pivotal trial is a multicenter, open label, randomized, non-comparative, parallel cohort study at approximately 25 top cancer centers in the United States that began dosing in December 2020. TRACON expects the trial to enroll 160 patients with UPS or MFS who have progressed following one or two lines of prior treatment and have not received an immune checkpoint inhibitor, with 80 patients enrolled into cohort A of treatment with single agent envafolimab and 80 patients enrolled into cohort B of treatment with envafolimab and Yervoy. The primary endpoint is ORR by blinded independent central review with duration of response a key secondary endpoint.

About TRC102

TRC102 (methoxyamine) is a novel, small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the National Cancer Institute through a Cooperative Research and Development Agreement (CRADA) and has orphan drug designation from the U.S. FDA in malignant glioma, including glioblastoma.

About TJ004309

TJ004309 is a novel, humanized antibody against CD73, an ecto-enzyme expressed on stromal cells and tumors that converts extracellular adenosine monophosphate (AMP) to adenosine, which is highly immunosuppressive. TJ004309 is currently being studied in an ongoing Phase 1 trial to assess safety and preliminary efficacy as a single agent and when combined with the PD-L1 checkpoint inhibitor Tecentriq in patients with advanced solid tumors.