On June 23, 2020 Sana Biotechnology, Inc. (Sana), focused on engineering cells as medicines for patients, reported the funding of all tranches of its initial financing, raising over $700 million (Press release, Sana Biotechnology, JUN 23, 2020, View Source [SID1234567820]).

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With this financing, Sana’s shareholders include ARCH Venture Partners, Flagship Pioneering, Canada Pension Plan Investment Board, Baillie Gifford, F-Prime Capital, Alaska Permanent Fund, the Public Sector Pension Investment Board, Bezos Expeditions, GV, Omega Funds, Altitude Life Science Ventures, and multiple unnamed institutional investors.

"Sana is dedicated to modulating genes in cells as well as replacing damaged cells in the body," said Steve Harr, Sana President and CEO. "The commitment from this group of long-term investors enables us to concentrate on making discoveries that overcome the most important challenges to making gene and cell therapies that improve the lives of a broad swath of patients. I am proud of our progress to date in turning our technologies into potential therapies for serious diseases such as cancer, central nervous system diseases, heart disease and various genetic disorders."

Proceeds from Sana’s financing will be used to advance discovery and development within the company’s core platforms, including gene delivery, immunology, stem cell biology, and gene modification and control. Some approaches include in vivo delivery of genetic payloads to specific cells, ex vivo genetic modifications that hide allogeneic cells from a patient’s immune system, and applying stem cell biology to make differentiated cells to replace missing or damaged tissue. Proceeds are expected to support IND-enabling and initial clinical studies for multiple therapeutic candidates, buildout of manufacturing capabilities, and expansion of the company’s portfolio of enabling technologies. They will also support the continued addition of top talent to Sana’s team.

On June 23, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported that it has entered into a collaborative agreement with Merck & Co., Inc., Kenilworth, NJ, USA (known as MSD outside the US and Canada) with the intent to initiate a randomized phase II trial to evaluate the combination of ONCOS-102, Keytruda (pembrolizumab), MSD’s anti-PD-1 therapy, and standard of care (SoC) chemotherapy in malignant pleural mesothelioma (Press release, Targovax, JUN 23, 2020, View Source [SID1234564004]).

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Recently, Targovax reported encouraging results from the ongoing phase I/II trial evaluating intra-tumoral ONCOS-102 treatment in addition to SoC (pemetrexed and cisplatin) in first and second line unresectable mesothelioma, see press release here. These data indicate a potential clinical benefit of ONCOS-102, particularly in first line patients. Importantly, clinical responses were associated with robust immune activation, T-cell infiltration and up-regulation of PD-L1, and, as such, suggest that patients may benefit from the addition of anti-PD-1 checkpoint blockade.

Following these efficacy and mechanistic findings, Targovax and MSD have agreed to initiate a collaboration trial evaluating the combination of ONCOS-102, KEYTRUDA and SoC in first line mesothelioma patients. The trial will be a randomized phase II of up to 100 patients comparing this investigational triple combination against Keytruda and SoC. There is strong interest to participate in the trial among key opinion leaders and investigators, and multiple centers in both the USA and EU will be participating. The aim is to start enrolling patients into the trial within twelve months.

Øystein Soug, CEO of Targovax, said: "We believe the clinical immune activation data we have seen so far provide a strong scientific rationale for adding anti-PD1 checkpoint blockade to the ONCOS-102 and chemotherapy combination in mesothelioma. Therefore, we are delighted that MSD has agreed to support us in exploring this hypothesis by providing KEYTRUDA supply for our next trial. KEYTRUDA is the market-leading checkpoint inhibitor and thus our preferred choice of partner. We are hopeful that the combination of ONCOS-102, pembrolizumab and chemotherapy will lead to improved outcomes for patients with this challenging disease who currently have few treatment alternatives".

On June 23, 2020 Sunesis Pharmaceuticals, Inc. (Nasdaq: SNSS) reported that the Company will not advance its non-covalent BTK inhibitor vecabrutinib into the planned Phase 2 portion of the Phase 1b/2 trial in adults with relapsed/refractory chronic lymphocytic leukemia (CLL) and other B-cell malignancies (Press release, Sunesis, JUN 23, 2020, View Source [SID1234561678]). The decision was made after assessing the totality of the data including the 500 mg cohort, the highest dose studied in the trial.

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"Although vecabrutinib continues to exhibit an excellent safety profile, there is insufficient evidence of activity in BTK-inhibitor resistant B-cell malignancies to advance the drug into the planned Phase 2 portion of the trial. One partial remission was observed after 11 treatment cycles in a CLL patient treated in Cohort 5 (300 mg BID) and a number of patients treated across the dose range explored (25 mg to 500 mg BID) saw stable disease; however, no other remissions have been observed," said Dayton Misfeldt, Interim Chief Executive Officer of Sunesis. "We will complete the Phase 1b and evaluate the best path forward for vecabrutinib. We are grateful for the patients and their families who participated in this trial, as well as the investigators and research staff at our trial sites."

Mr. Misfeldt continued: "We are shifting our resources and development focus to our first-in-class PDK1 inhibitor SNS-510. SNS-510 inhibits PI3K-dependent and PIP3-independent pathways important in both solid and hematologic malignancies. We remain on track to file an IND by the end of 2020 and expect to present additional preclinical findings at a medical meeting in the second half of the year. We expect that our current cash resources are sufficient to fund the company into 2021."

Vecabrutinib Phase 1b/2 Clinical update. Currently, five patients enrolled in cohorts 5-7 remain on treatment and continue to be followed. Vecabrutinib is very well tolerated across the dose range investigated.

Cohort 7 (500mg BID): Three (2 CLL, 1 MCL) of six treated patients had stable disease at first response assessment (beginning of cycle 4). One of the CLL patients is in Cycle 7, the MCL patient is in cycle 6 and one CLL patient was determined to have progressive disease after 6 cycles. We did not see a reduction in tumor burden in any of the patients with stable disease.

Cohort 6 (400mg BID): Of 6 patients treated, 2 CLL patients remain on study in cycle 9, one with stable disease and the other who had progressive disease at first assessment but continues to derive clinical benefit. One CLL patient who had stable disease with a 48% reduction in tumor burden at first assessment progressed in cycle 7.

Cohort 5 (300mg BID): One CLL patient remains on treatment in cycle 12 with a partial response observed at third response assessment done at the start of cycle 12.
About SNS-510

SNS-510 is a PDK1 inhibitor licensed from Millennium Pharmaceuticals, Inc. ("Takeda Oncology"), a wholly-owned subsidiary of Takeda Pharmaceutical Company Limited. SNS-510 interaction with PDK1 inhibits both PI3K signaling and PIP3-independent pathways integral to many malignancies, and PDK1 can also be overexpressed in breast, lung, prostate, hematologic and other cancers. Evaluation of SNS-510 in the Eurofins Oncopanel, a panel of >300 genomically profiled cancer cell lines from diverse tissue origins, indicated that CDKN2A-mutated tumors are particularly sensitive to SNS-510. CDKN2A alterations are common in human cancers and may prove to be useful biomarkers for broad investigation of SNS-510 as a monotherapy and in combination with other anticancer agents. Sunesis is conducting an Investigational New Drug ("IND")-enabling program for SNS-510 and plan to file an IND by the end of 2020.

On June 23, 2020 Greenwich LifeSciences, a Phase 3 biotech developing immunotherapies for breast cancer, reported that terms for its IPO on Tuesday (Press release, Greenwich LifeSciences, JUN 23, 2020, View Source [SID1234561462]).

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The Stafford, TX-based company plans to raise $21 million by offering 2.7 million shares (63% insider) at a price range of $7.50 to $8.50. At the midpoint of the proposed range, Greenwich LifeSciences would command a fully diluted market value of $106 million.

The company is developing GP2, an immunotherapy designed to prevent the recurrence of breast cancer following surgery. GP2 is a 9 amino acid transmembrane peptide of the HER2/neu protein. In a Phase 2b clinical trial completed in 2018, no recurrences were observed in the HER2/neu 3+ adjuvant setting after median 5 years of follow-up, if the patient received the 6 primary intradermal injections over the first 6 months. The company is planning to commence a Phase 3 trial in 2020.

Greenwich LifeSciences was founded in 2006 and plans to list on the Nasdaq under the symbol GLSI. Aegis Capital Corp. is the sole bookrunner on the deal.

The article Breast cancer biotech Greenwich LifeSciences sets terms for $21 million IPO originally appeared on IPO investment manager Renaissance Capital’s web site renaissancecapital.com.

On June 23, 2020 Oncotarget reported that to examine the role of RSK in AML, the authors analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK (Press release, EurekAlert!, JUN 23, 2020, View Source [SID1234561423]). BI-D1870 treatment increased the G2/M population and induced apoptosis in Acute Myeloid Leukemia cell lines and patient Acute Myeloid Leukemia cells .

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Therefore, the authors investigated whether BI-D1870 potentiates the anti-leukemic activity of vincristine by targeting mitotic exit.

Combination treatment of BI-D1870 and vincristine synergistically increased mitotic arrest and apoptosis in acute leukemia cells.

These data show that BI-D1870 induces apoptosis of AML cells alone and in combination with vincristine through blocking mitotic exit, providing a novel approach to overcoming vincristine resistance in AML cells.

"Data show that BI-D1870 induces apoptosis of AML cells alone and in combination with vincristine through blocking mitotic exit"
Dr. Kathleen M. Sakamoto from Stanford University School of Medicine said, "Acute myeloid leukemia (AML) is a genetically and phenotypically heterogeneous hematologic malignancy characterized by the accumulation of immature myeloid blasts with resultant peripheral blood cytopenia."

Treatment of cells with microtubule targeting agents, including paclitaxel and the vinca alkaloid vincristine, blocks the proper formation of the mitotic spindle through inhibition of microtubule dynamics, resulting in the prolonged mitotic arrest of cancer cells.

MTAs-treated mitotic arrested cells may undergo apoptosis in mitosis, however, the rapid degradation of Cyclin B due to an insufficient SAC leads to the mitotic slippage into tetraploid G1 stage in resistant cells.

Though vinca alkaloid microtubule-destabilizing compounds have shown clinical efficacy against various hematological malignancies and were included in combination chemotherapy of the VAPA study, they are not currently used in induction chemotherapy for AML due to their high toxicity against lymphoid cells and rapid degradation by myeloperoxidase in AML cells.

In this study, they demonstrate that BI-D1870, a potent inhibitor of RSK, induces mitotic arrest, and apoptosis in AML cells without inhibiting CDC2 and CDC25C. Furthermore, BI-D1870 synergizes with vinca alkaloid vincristine in AML cells, suggesting that inhibition of mitotic exit with BI-D1870 could be a promising novel approach for AML therapy in combination with MTAs.

The Sakamoto Research Team concluded in their Oncotarget Research Paper that BI-D1870 is a reversible pan-RSK inhibitor, showing > 500-fold higher activity for RSK than other AGC kinases.

BI-D1870 also inhibits the activity of PLK1, Aurora-B, MELK, PIM3, MST2, and GSK3β at higher concentrations than for RSK. BI-D1870 and BRD7389 have been reported to inhibit proliferation and significantly increase the G2/M population in melanoma cells.

BI-D1870 does not have proper physicochemical properties for clinical application.

Future structure-activity relationships study for BI-D1870 is required to improve solubility and pharmacokinetic profiles for in vivo preclinical and clinical studies.