On August 19, 2021 Gilead Sciences reported that Researchers with the Georgia Institute of Technology recently published work in Nature Biomedical Engineering that describes several new approaches to improving CAR-T, particularly for solid tumors (Press release, Gilead Sciences, AUG 19, 2021, View Source [SID1234586782]).

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CAR-T therapy, such as Gilead Sciences’ Yescarta (axicabtagene ciloleucel) for non-Hodgkin lymphoma, acute lymphoblastic leukemia, mantle cell lymphoma and other indications, and Novartis’ Kymriah (tisagenlecleucel), approved for acute lymphoblastic leukemia, chronic lymphoid leukemia, diffuse large B-cell lymphoma, as well as others, are very effective for hematologic cancers. However, getting CAR-T to work in solid tumors has been a tougher nut to crack.

In CAR-T (chimeric antigen receptor T-cell) therapy, T-cells are isolated from a cancer patient, engineered in the laboratory by adding a gene for a chimeric antigen receptor (CAR), grown, then infused back into the patient. There, they become a sort of living therapy highly tuned to attack the patient’s cancer.

"These therapies have proven to be remarkably effective for patients with liquid tumors — so, tumors that are circulating in the blood, such as leukemia," Gave Kwong, associate professor in the Wallace H. Coulter Department of biomedical engineering at Georgia Tech and Emory, and senior study investigator told Genetic Engineering & Biotechnology News. "Unfortunately, for solid tumors — sarcomas, carcinomas — they don’t work well. There are many different reasons why. One huge problem is that the CAR T-cells are immunosuppressed by the tumor microenvironment."

Kwong’s team is working to change the microenvironment to improve CAR-T in these cancers. One approach is to create an on-off switch that is sensitive to heat.

Earlier work conducted by his research group precisely targets tumors with a local deposit of heat, which activates the CAR-T cells inside the tumor. To create heat, they used laser pulses from outside the body. Gold nanorods that are delivered to the tumor convert the light waves into localized heat, increasing the temperature to 40 to 42 degrees C, which activates the switch but doesn’t harm healthy tissues or the T-cells.

In addition to genetically engineering the CAR-T cells to respond to that switch, they have also redesigned them to manufactures immune stimulatory molecules. These cytokines and bispecific T-cell engagers are controlled carefully.

Kwong said, "These cancer-fighting proteins are really good at stimulating CAR T-cells, but they are too toxic to be used outside of tumors. They are too toxic to be delivered systemically. But with our approach, we can localize these proteins safely. We get all the benefits without the drawbacks."

The study was conducted on mice. The research led to a 60-fold-higher expression of a reporter transgene without affecting the CAR-T cells’ proliferation, migration, and cytotoxicity. The system cured cancer in the mice, shrinking tumors and preventing relapse.

The researchers say that when they test it in humans, instead of the laser, they will use focused ultrasound, which is noninvasive while targeting any location in the body. Lasers don’t penetrate far enough into the body to be a practical approach in humans.

"So," Kwong said, "if you have a deep-seated malignant tumor, that would be a problem. We want to eliminate problems."

On August 19, 2021 Sonnet BioTherapeutics Holdings, Inc. (NASDAQ:SONN) ("Sonnet" or the "Company"), a biopharmaceutical company developing innovative targeted biologic drugs, reported the pricing of an underwritten public offering of 35,294,117 shares of common stock or common stock equivalents (which includes pre-funded warrants to purchase shares of common stock in lieu of shares of common stock) and investor warrants to purchase up to an aggregate of 35,294,117 shares of common stock (Press release, Sonnet BioTherapeutics, AUG 19, 2021, View Source [SID1234586778]). Each share of common stock (or pre-funded warrant in lieu thereof) is being sold together with one investor warrant to purchase one share of common stock at a combined offering price of $0.85, for total gross proceeds of approximately $30.0 million, before underwriting discounts and commissions and offering expenses payable by Sonnet. The investor warrants have an exercise price of $0.85 per share. The offering is expected to close on or about August 24, 2021, subject to the satisfaction or waiver of customary closing conditions.

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BTIG is acting as the sole book-running manager in connection with the offering and Chardan is acting as lead manager.

The Company has also granted the underwriters a 30-day option to purchase up to 5,294,117 additional shares of its common stock and/or investor warrants to purchase up to 5,294,117 additional shares of its common stock, in any combination thereof, at the public offering price, less underwriting discounts and commissions, to cover over-allotments, if any.

Sonnet anticipates using the net proceeds from the offering for research and development, including clinical trials, working capital and general corporate purposes.

The securities will be offered pursuant to a registration statement on Form S-1, as amended (File No. 333-258092), which was declared effective by the Securities and Exchange Commission (the "SEC") on August 19, 2020. The offering is being made solely by means of a prospectus. A preliminary prospectus relating to and describing the terms of the offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus and, when available, copies of the final prospectus relating to this offering can be obtained at the SEC’s website at www.sec.gov or from BTIG, LLC, Attention: Equity Capital Markets, 65 East 55th Street, New York, NY 10022, by calling (212) 593-7555 or by e-mail at [email protected].

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

On August 19, 2021 NuCana plc (NASDAQ: NCNA) reported its financial results for the second quarter ended June 30, 2021 and provided an update on its broad clinical program with its transformative ProTide therapeutics (Press release, Nucana BioPharmaceuticals, AUG 19, 2021, View Source [SID1234586776]).

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As of June 30, 2021, NuCana had cash and cash equivalents of £73.4 million compared to £78.6 million at March 31, 2021 and £87.4 million as of December 31, 2020. NuCana continues to advance its various clinical programs and reported a net loss of £9.1 million for the quarter ended June 30, 2021, as compared to a net loss of £6.1 million for the quarter ended June 30, 2020. Basic and diluted loss per share was £0.17 for the quarter ended June 30, 2021, as compared to £0.19 per share for quarter ended June 30, 2020.

"It has been a productive first half of 2021 with our release of important non-clinical and clinical data announcements. These include data from the NuTide:302 Phase Ib study of NUC-3373 in patients with advanced colorectal cancer as well as from the NuTide:701 Phase I study of NUC-7738 in patients with advanced solid tumors," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "These data presentations, made at several medical conferences, continue to support the favorable clinical profile we have observed to date and the broad potential of our ProTide technology."

Mr. Griffith continued: "As we look ahead to the second half of the year, we anticipate presenting additional clinical data from NUC-3373 and NUC-7738. Despite the COVID-19 pandemic, we remain on track to recruit sufficient patients in 2021 in the ongoing NuTide:121 Phase III clinical study of Acelarin combined with cisplatin as a first-line treatment for patients with advanced biliary tract cancer to enable the first interim analysis in 2022. We are hopeful that this could enable us to submit an NDA in the United States under the FDA’s accelerated approval program. We are also on track with other key milestones, including the initiation this year of a Phase III study of NUC-3373 in combination with other agents for patients with colorectal cancer."

Mr. Griffith also noted that NuCana has established preliminary objectives for the first half of 2022: "We are looking forward to 2022, which will be an important and active year for NuCana. With Acelarin, we anticipate announcing whether the NuTide:121 study has achieved the overall response rate objective at the first interim analysis in the first half of 2022. Additionally, based on the encouraging data seen to date with NUC-3373 and 5-FU’s broad usage in oncology, we anticipate initiating in 2022 a Phase Ib basket study of NUC-3373 in combination with other agents in a variety of solid tumors to identify further indications to target. We also expect to announce in 2022 data from the Phase II study of NUC-7738, which is anticipated to start later in 2021."

Mr. Griffith concluded: "Lastly, it is my pleasure to welcome Dr. Jeffrey Bloss to NuCana as our new Chief Medical Officer. Jeff brings more than two decades of relevant oncology experience leading clinical development and medical affairs at a number of companies. Over his career, he has been a key member of the teams responsible for the development, approval and commercialization of over ten successful oncology drugs including Gemzar, Tarceva, Sorafenib, Tykerb and Xtandi. His experience and contributions will be invaluable to NuCana as we continue to advance our pipeline of novel ProTides through the clinic and towards commercialization."

Anticipated Milestones: H2 2021 & H1 2022

•Acelarin (a ProTide transformation of gemcitabine)

ºIn 2021, NuCana expects to reach enrollment of at least 418 evaluable patients to enable the first interim analysis in 2022 of the Phase III study of Acelarin combined with cisplatin as a first-line treatment for patients with advanced biliary tract cancer; and
ºIn the first half of 2022, NuCana expects to announce whether the overall response rate objective for the first interim data from this Phase III study has been met, which may enable an NDA submission in the United States under the FDA’s accelerated approval program.

•NUC-3373 (a ProTide transformation of 5-FU)

In 2021, NuCana expects to:

ºReport data from the Phase Ib study (NuTide:302) of NUC-3373 in combination with other agents with which 5-FU is typically combined, such as leucovorin, oxaliplatin and irinotecan in patients with advanced colorectal cancer;
ºInitate and report data from the Phase Ib expansion / Phase II study of NUC-3373 in combination with other agents for patients with colorectal cancer;
ºInitiate a Phase III study of NUC-3373 in combination with other agents for patients with colorectal cancer; and
ºReport data from the Phase I study (NuTide:301) of NUC-3373 in patients with advanced solid tumors.
In the first half of 2022, NuCana expects to:
ºInitiate a Phase Ib basket study of NUC-3373 in combination with other agents in a variety of solid tumors; and
ºExpand the Phase Ib / Phase II study to include second-line colorectal cancer patients, as well as evaluate NUC-3373 in combination with monoclonal antibodies such as bevacizumab (Avastin).

•NUC-7738 (a ProTide transformation of 3’-deoxyadenosine)

In 2021, NuCana expects to:

ºReport data from the Phase I study (NuTide:701) of NUC-7738 in patients with advanced solid tumors; and
ºInitiate a Phase II study of NUC-7738 in patients with solid tumors.

In the first half of 2022, NuCana expects to:

ºAnnounce data from the Phase II study of NUC-7738 in patients with solid tumors.

On August 19, 2021 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a global biotech company focused on the development of therapies for difficult-to-treat hematological diseases, reported the second quarter 2021 (Press release, Oncopeptides, AUG 19, 2021, View Source [SID1234586773]).

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Financial overview April-June

Net sales amounted to SEK 66.4 M (0.0)
Operating loss amounted to SEK 344.8 M (loss: 399.3)
Loss for the period was SEK 24.1 M (loss: 401.0)
Loss per share, before and after dilution, was SEK 0.32 (loss: 6.79)
Cash and cash equivalents amounted to SEK 999.4 M (937.8) on June 30
Financial overview January-June

Net sales amounted to SEK 85.7 M (0.0)
Operating loss amounted to SEK 692.2 M (loss: 696.2)
Loss for the period was SEK 258.8 M (loss: 698.4)
Loss per share, before and after dilution, was SEK 3.63 (loss: 12.20)
Cash and cash equivalents amounted to SEK 999.4 M (937.8) on June 30
Significant events April-June

An application for conditional marketing authorization of melflufen in the EU was submitted in April
Topline results from the phase 3 OCEAN study were announced in May
Patient enrollment in the phase 2 PORT study was completed in May
A German affiliate was established in May
Clinical abstracts on melflufen was presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in June
New clinical and preclincal melflufen data was presented at the European Hematology Association (EHA) (Free EHA Whitepaper) meeting in June
Significant events after the reporting period

Updated results from the phase 3 OCEAN study were announced on July 8: melflufen met the primary endpoint of superior PFS
Overall survival data, also released on July 8, led to the FDA requesting a partial clinical hold of all clinical studies with melflufen, pending further investigation
FDA issued a safety alert to patients and health care professionals on July 28, regarding an increased risk of death associated with Pepaxto in the OCEAN study.

Conference call for investors, analysts and the media

Investors, financial analysts and media are invited to participate in a webcast with a Q&A session at 12:00 CEST. The event will be hosted by CEO, Marty J Duvall, CMO, Klaas Bakker and CFO, Anders Martin-Löf.

The webcast will be streamed via this link which can also be found on the website: www.oncopeptides.com.

This information is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation and the Securities Markets Act. The information was submitted for publication, through the agency of the contact persons set out above, at 07:00 CET on August 19, 2021.

On August 19, 2021 Medivir AB reported that Interim Report January – June 2021 (Press release, Medivir, AUG 19, 2021, View Source;interim-report-january–june-2021-301358672.html [SID1234586772])

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April – June
Financial summary for the quarter

Net turnover amounted to SEK 0.9 (4.0) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -17.1 (-12.4) million. Basic and diluted earnings per share amounted to SEK -0.35 (-0.52) and SEK -0.35 (-0.52) respectively.
Cash flow from operating activities amounted to SEK -21.9 (-23.3) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 247.8 (94.9) million.
Significant events during the quarter

On April 16, it was announced that Magnus Christensen had been appointed interim CEO of Medivir. He took up his new role in connection with Medivir’s AGM on May 5, 2021.
On April 19, it was announced that the overall results from the first part of the phase Ib study with MIV-818 were positive with a good safety and tolerability profile. Thus, the starting dose for the second part of the phase Ib study could be determined.
In May, positive results from an investigator-initiated phase II clinical study of remetinostat in patients with squamous cell carcinoma (SCC) were released on clinicaltrials.gov.
In May, the design for the upcoming phase 1b/2a combination study with the company’s leading candidate drug, MIV-818 against liver cancer, was presented. In the study, MIV-818 will be administered in two combinations, with either lenvatinib, a tyrosine kinase inhibitor, or pembrolizumab, an anti-PD-1 checkpoint inhibitor.
January – June
Financial summary for the period

Net turnover amounted to SEK 10.8 (11.4) million.
The loss before interest, tax, depreciation and amortization (EBITDA) amounted to SEK -24.3 (-33.1) million. Basic and diluted earnings per share amounted to SEK -0.57 (-1.49) and SEK -0.57 (-1.49) respectively.
Cash flow from operating activities amounted to SEK -23.3 (-40.0) million.
Liquid assets and short-term investments at the end of the period amounted to SEK 247.8 (94.9) million.
Significant events after the end of the period

In July, Malene Jensen was appointed Vice President Clinical Development. She will assume her role on September 6, 2021.
In August, it was announced that data from the MIV-818 phase 1b study will be presented at the ESMO (Free ESMO Whitepaper) Congress in September.
In August, the positive results from the phase II study with remetinostat against basal cell carcinoma were published in the scientific journal Clinical Cancer Research.
In August, it was announced that Medivir, through a renegotiated multi-party agreement, strengthens the business development potential for remetinostat.
Conference call for investors, analysts and the media
The Interim Report January – June 2021 will be presented by Medivir’s interim CEO, Magnus Christensen.

The conference call will also be streamed via a link on the website: www.medivir.com
The presentation will be available on Medivir’s website after completion of the conference.

CEO’s message
The clinical development of MIV-818 remains in focus. Positive topline results in the phase 1b monotherapy study. The design determined for the phase 1b/2a combination study in the clinical MIV-818 program.

Medivir’s central task is to advance the clinical program for our leading candidate drug MIV-818, which has the potential to be a liver-directed, orally administered drug that can help patients with various cancers of the liver. This work has also characterized our operations also in the past quarter.

In April we were able to announce that the results from the first part of the phase 1b study with MIV-818 were positive with a good safety and tolerability profile. Thereby, we were also able to determine the starting dose for the second part of the study, where we combine MIV-818 with standard treatment. Data from the first part of the phase 1b study will be presented at the ESMO (Free ESMO Whitepaper) scientific conference in September.

Due to its unique mechanism of action, MIV-818 is attractive to combine with a multitude of other drugs for the treatment of hepatocellular carcinoma (HCC). We have been working on refining the design for the next step in the clinical program, the upcoming phase 1b/2a combination study with MIV-818, and at the end of May we presented how the study is structured. MIV-818 will be administered in two combinations, either with lenvatinib, a tyrosine kinase inhibitor, or with pembrolizumab, an anti-PD-1 checkpoint inhibitor.

The study is an open-label, multi-center phase 1b/2a study that begins with a dose escalation part to determine the recommended phase 2 dose (RP2D). This is followed by the expansion study (phase 2a) with an initial evaluation of the safety and efficacy of the combinations of MIV-818 with lenvatinib or pembrolizumab. The study will include patients with HCC who have progressed on, or are intolerant of, first line standard therapy.

We plan to recruit the first patient for the combination study in the second half of 2021. However, we cannot guarantee that the Covid-19 pandemic will not affect our schedule.

MIV-818 is proprietary and wholly owned by Medivir, i.e. we do not have to pay any future milestones or royalties to any third party.

We have two more drug development projects in the clinical development phase, remetinostat, and MIV-711. Medivir does not conduct clinical development of these projects on its own, but instead seeks partners for further development.

During the quarter, positive results were published from an investigator-initiated clinical phase II study of remetinostat in patients with squamous cell carcinoma (SCC). The study was conducted at the Stanford University School of Medicine in California, USA. The primary objective of the study was to assess the effects of topical remetinostat on biopsy-proven SCC and SCC in situ tumors. In August, the positive results from the phase II study with remetinostat in patients with BCC were also published in the scientific journal Clinical Cancer Research.

The results are very promising and provide further support for the potential of remetinostat as a treatment for a number of skin-associated cancers in addition to cutaneous T-cell lymphoma (CTCL). Medivir renegotiated in August a multi-party agreement with the originators of remetinostat and TetraLogic Pharmaceuticals Corporation and The Leukemia & Lymphoma Society regarding the financial obligations for remetinostat in order to create better conditions for business development.

Medivir’s birinapant project, for the treatment of solid tumors, was outlicensed to the American company IGM Biosciences at the beginning of the year. IGM has the global and exclusive rights to develop birinapant. According to IGM’s Q2 report, they plan to initiate clinical trials with birinapant in combination with their proprietary antibody IGM-8444 during 2021.

At Medivir’s AGM on May 5, former CEO Yilmaz Mahshid was elected new board member and Uli Hacksell was elected chairman of the board. This guarantee continued scientific vitality and business acumen in the Board’s work.

In July, Malene Jensen was recruited as Vice President Clinical Development and a member of the company’s management team. With extensive experience in clinical development, Malene will focus on the clinical studies with MIV-818.

I am really impressed by the determination and dedication shared by all Medivir employees. The goal is to develop an effective drug against liver cancer through MIV-818. Given that this work continues to show good results, it could make a big difference for patients and for healthcare and thus also for the company’s shareholders.