On June 22, 2020 Targovax ASA (OSE: TRVX), a clinical stage immuno-oncology company developing oncolytic viruses to target hard-to-treat solid tumors, reported 12-month efficacy and immunological data from the randomized phase I/II trial of ONCOS-102 in combination with standard of care chemotherapy in malignant pleural mesothelioma (MPM) (Press release, Targovax, JUN 22, 2020, View Source [SID1234564002]).

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The trial is an open label, exploratory phase I/II trial adding ONCOS-102 to standard of care (SoC) chemotherapy (pemetrexed/cisplatin) in first and second (and later) line MPM to assess safety, immune activation and clinical efficacy vs SoC only. In total, 31 patients have been treated in the trial, with 20 patients in the experimental group receiving the ONCOS-102 and SoC combination, and 11 patients in a control group receiving SoC only. The 31 patients have now completed the 12-month follow-up. The first set of data was reported in January 2020, see press release here, with an update in May 2020, see press release here.

The median Progression Free Survival (mPFS) for ONCOS-102 treated first line patients remains at 8.9 months, which is identical to the previously reported early data. mPFS for the control group first line patients treated with SoC chemotherapy only is 7.6 months. The first line mPFS data continues to compare favorably to SoC historical controls, which have shown mPFS of 5.7-7.3 months[1]. As there is now longer follow-up and few censored patients left in the PFS analysis, the updated figures can be considered close to final.

The 12-month survival rate was 64% in the first line ONCOS-102 treated patients, compared to 50% in the first line control group treated with SoC chemotherapy only (median Overall Survival is too early to report). The patients continue to be followed and updated Overall Survival (OS) figures will be published as they mature. This 64% 12-month survival rate is encouraging compared to the control group, but there are few historical control reference points. Recently, at ASCO (Free ASCO Whitepaper) 2020, results from a first line mesothelioma trial assessing SoC chemotherapy in combination with the anti-PD-L1 checkpoint inhibitor durvalumab showed a 70% 12-month survival rate. This suggests that ONCOS-102 alone plus SoC chemotherapy may already achieve a level of benefit close to that observed with checkpoint inhibition plus SoC chemotherapy. It is expected that addition of checkpoint inhibition to ONCOS-102 and Soc will provide even further clinical benefit due to engagement of distinct and complementary biological mechanisms. As such, Targovax’s future clinical development of ONCOS-102 will focus on first line mesothelioma with the triple combination of a checkpoint inhibitor, ONCOS-102 and SoC. A randomized phase II trial is currently being planned in collaboration with a pharma partner.

Tumor biopsy immunohistochemistry and gene expression analyses from the present trial confirm the predicted mode of action of ONCOS-102. Importantly, profound innate and adaptive immune activation is observed in the ONCOS-102 treated patients compared to the control group, and this immune activation is associated with better clinical outcome. The immune activation is hallmarked by an increase in intra-tumoral cytotoxic T-cells and upregulation of adaptive immunity and cytotoxicity related gene expression, in parallel with polarization from M2 to M1 macrophage phenotype and upregulation of PD-L1 expression, indicating that ONCOS-102 is driving a favorable remodeling of the tumor microenvironment. This powerfully demonstrates the immune activation potential of ONCOS-102 far beyond what is achieved by chemotherapy alone and suggests that patients may be effectively sensitized to treatment with an anti-PD1/L1 antagonist, thereby providing strong scientific rationale for the combination of ONCOS-102 and checkpoint inhibition in first line mesothelioma.

Dr. Magnus Jäderberg, Chief Medical Officer of Targovax, said: "We are very pleased to see the encouraging first line PFS data holding up in the 12-month analysis, with early signs of positive survival outcomes. We are particularly excited to observe a broad and profound immune activation in the ONCOS-102 treated patients, which confirms the proposed mode of action. ONCOS-102 treatment clearly drives a favorable remodeling of the tumor microenvironment, and this remodeling is linked to better clinical outcomes. This immune activated tumor micro-environment provides the key scientific rationale and an ideal backdrop for combination treatment with a checkpoint inhibitor. These data set us up perfectly to move forward with a trial combining ONCOS-102 and a checkpoint inhibitor, which we believe will release the full potential of immunotherapy in this hard-to-treat patient population".

On June 22, 2020 AIMM, a privately-held biopharmaceutical company, reported it has presented preclinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2020 Virtual Annual Meeting from its antibody programs in oncology using a rich pipeline of tumor- specific antibodies from cured cancer patients (Press release, AIMM Therapeutics, JUN 22, 2020, View Source [SID1234561293]).

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"Recognizing that cured cancer patients have benefited, directly or indirectly, from a robust and specific antibody response, AIMM has set out to select those functional antibodies as a starting point for its drug development programs," said John Womelsdorf, Ph.D., chief executive officer of AIMM Therapeutics. "AIMM is perfectly positioned to advance this approach; firstly, through our ability to interrogate the entire B cell repertoire of the surviving patient and identify novel targets and anti-cancer antibodies using our AIMSelect platform. And, secondly, we are able to potentiate these antibodies for use as therapies through our AIMProve platform to leverage the unique biology that was underlying the original donor’s successful clinical response."

AIMM has a pipeline of multiple drug candidates that bind to novel cancer targets and epitopes. The company’s lead asset, AT1412, is a CD9-targeted antibody derived from a stage 4 melanoma patient with brain metastasis who was successfully treated with autologous T-cell based immunotherapy and is still tumor-free after 13 years despite having an aggressive cancer. AT1412 is going through the last stages of preclinical development for B-cell lymphoblastic leukemia/lymphoma (B-ALL) and CD9+ solid tumors, such as melanoma, gastric, breast, and esophageal cancers. Preclinical data from studies of AT1412 in B-ALL and melanoma tumor models show monotherapy treatment induced full tumor rejection that in the case of melanoma can be further sustained in combination with nivolumab. Two posters presented at AACR (Free AACR Whitepaper) demonstrate the potential for AT1412 to be a potent antibody capable of inducing cell death and facilitating the trafficking of immune cells into the tumor microenvironment.

Additionally, several antibody candidates, such as CD3-bispecific/ADC/CAR-T assets, are in lead optimization and could provide for multiple non-dilutive partnering opportunities and co-development collaborations. AT1413, isolated from an M5 acute myeloid leukemia patient that underwent allograft stem cell transplantation, has the potential to be formatted into a CD3-bispecific, ADC or CAR-T. Another poster presented at AACR (Free AACR Whitepaper) describes two different bispecific T-cell engaging forms of AT1413 that induce strong anti-tumor cytotoxic activities in AML and solid tumors like melanoma and breast carcinoma. A fourth poster presented at the AACR (Free AACR Whitepaper) annual meeting reviews AT1636, an antibody targeting a cancer- specific glyco-modified antigen, which was retrieved from a patient with Lynch syndrome.

Hans van Eenennaam, Ph.D., who joined AIMM Therapeutics in 2019 as its chief scientific officer and is credited as a co-inventor of pembrolizumab, added, "Using patient-derived antibodies as therapeutics represents an exciting approach to drug development because they are unlocking novel targets and mechanisms of action. As exemplified by our AT1412 (anti-CD9 antibody), we have identified that this patient-derived antibody induces antibody-mediated tumor kill and promotes immune cell penetration into the tumor. Our technologies were initially developed and validated for applications in infectious disease, resulting in the out licensing of a product candidate for respiratory syncytial virus to MedImmune that is now in Phase 3 development. Following years of groundbreaking experience in the field led by my predecessor and founder of the company Hergen Spits, professor at the Academic Medical Center in Amsterdam, we are now applying our evolved and highly selective antibody technologies to treat cancer. Our unique and proprietary technology allows us to interrogate every memory B-cell in both human blood and tumors for anti-cancer reactivity. Together with our rich tradition of cutting-edge immunology, we are uniquely positioned to identify targets on both hematological and solid tumors that have not been previously identified before."

AACR Presentations on June 22, 2020
Poster 531, Session: Antibody Technologies
AT1412, a patient-derived antibody in development for the treatment of cd9-positive precursor b-acute lymphoblastic leukemia

Poster 532, Session: Antibody Technologies
A patient-derived anti-CD9 antibody induces tumor rejection and synergistically enhances anti-PD1 activity

Poster 542, Session: Antibody Technologies
T-cell engager bispecific formats of an AML patient-derived antibody targeting a unique sialylated CD43 epitope induce kill of melanoma cells in vitro and in vivo

Poster 5163, Session: Antibody Technologies
A colon cancer survivor-derived antibody recognizes a previously unidentified truncated, O-mannosylated 70kDa variant of E-cadherin

On June 22, 2020 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported the entry into an underwriting agreement relating to the sale of 2,666,667 shares of its common stock at an offering price of $3.75 per share, less underwriting discounts and commission (Press release, Celsion, JUN 22, 2020, View Source [SID1234561312]). The gross proceeds from the offering will be $10 million, before deducting underwriting discounts and commissions and estimated offering expenses. The shares of common stock are being sold to both existing and new institutional investors of the Company. The offering is expected to close on June 24, 2020, subject to satisfaction of customary closing conditions.

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Oppenheimer & Co. Inc. is acting as the sole underwriter for the offering.

Celsion intends to use the net proceeds for clinical development of our product candidates, working capital and other general corporate purposes.

This shares are being offered by Celsion pursuant to an effective shelf registration statement on Form S-3 (File No. 333-227236), previously filed with the Securities and Exchange Commission (SEC) on September 7, 2018 and declared effective on October 12, 2018. A prospectus supplement and the accompanying prospectus relating to and describing the terms of the offering will be filed with the SEC, and will be available on the SEC’s website at View Source or by contacting Oppenheimer & Co. Inc. at 85 Broad Street, 26th Floor, New York, NY 10004, Attention: Equity Syndicate Prospectus Department, by e-mail at [email protected] or by calling (212) 667-8055.

On June 22, 2020 Precigen, Inc., a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported preclinical data for its innovative investigational PRGN-3005 UltraCAR-T in patients with advanced, recurrent platinum resistant ovarian, fallopian tube or primary peritoneal cancer has been published as an e-poster and accompanying audio presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II (Press release, Precigen, JUN 22, 2020, View Source [SID1234561328]). The e-poster presentation titled PRGN-3005 UltraCAR-T: Multigenic CAR-T Cells Generated Using Non-viral Gene Delivery and Rapid Manufacturing Process for the Treatment of Ovarian Cancer (Abstract 6593) is part of the Immunology/Adoptive Cell Therapy session and is accessible on the AACR (Free AACR Whitepaper) e-poster website.

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Traditional methods for CAR-T cell manufacturing involve the use of viral vectors and ex vivo cell expansion at centralized manufacturing facilities, contributing to potentially high costs and extended waiting periods. Precigen’s UltraCAR-T platform, in contrast, is based upon a non-viral multigene delivery system combined with a rapid, decentralized manufacturing process without ex vivo expansion. Following isolation of the patient’s own T cells after blood draw, non-viral gene transfer occurs overnight at the medical center’s cGMP facility. The next day, UltraCAR-T cells are infused into the patient.

PRGN-3005 is an autologous CAR-T treatment simultaneously expressing three gene products, which results in a uniform, homogenous CAR-T cell therapy: 1) CAR to specifically target the unshed portion of Mucin 16 (MUC16), which is overexpressed on over 80% of ovarian tumors with limited expression found in healthy tissues; 2) membrane-bound IL-15 (mbIL15) to provide improved UltraCAR-T persistence and maintenance of preferred stem cell like memory phenotype; and 3) a kill switch to eliminate the CAR-T cells, if needed.

Preclinical data demonstrate the specificity and efficacy of using the rapidly manufactured PRGN-3005 UltraCAR-T cells for the treatment of ovarian tumors. Specifically, a single administration of PRGN-3005 showed significantly superior expansion and preferred memory phenotype of UltraCAR-T in vivo and significantly superior efficacy compared to traditional CAR-T resulting in all PRGN-3005 treated mice becoming tumor-free. Furthermore, rechallenging these tumor-free mice three months later with ovarian tumors for a second time (to simulate tumor relapse) led to the elimination of tumor burden without additional PRGN-3005 UltraCAR-T treatment. These data demonstrate the potential of UltraCAR-T cells to persist long-term in vivo, prevent CAR-T cell exhaustion, and mount a durable anti-tumor response with the ability to continue to respond upon tumor rechallenge.

"We are pleased to be able to share the preclinical data for PRGN-3005 that led to the IND clearance and initiation of the Phase I study," said Helen Sabzevari, PhD, President and CEO of Precigen. "Our preclinical results demonstrate that PRGN-3005 UltraCAR-T administered one day after non-viral gene transfer has superior anti-tumor efficacy and persistence compared to traditional CAR-T cells and represents a promising opportunity for ovarian cancer treatment. We look forward to sharing the first clinical data for PRGN-3005 in the second half of 2020."

Based on these preclinical results, the FDA approved the IND application, and the first-in-human PRGN-3005 Phase I clinical trial for advanced ovarian cancer is currently under way (clinical trial identifier: NCT03907527). The PRGN-3005 UltraCAR-T Phase I clinical study is an open-label, dose escalation study to evaluate the safety and maximal tolerated dose of PRGN-3005 UltraCAR-T delivered by intraperitoneal infusion (IP) or intravenous infusion (IV). The study population includes patients with advanced stage (III/IV) recurrent ovarian, fallopian tube, and primary peritoneal cancer who are platinum-resistant and have progressed after receiving standard-of-care therapies or are not eligible to receive available therapies with known clinical benefit.

About Ovarian Cancer
Worldwide, nearly 300,000 women are diagnosed with ovarian cancer every year1 with approximately 22,000 of them in the US2. Since early ovarian cancer is often without obvious symptoms, the disease is frequently diagnosed at an advanced stage where cancer has spread to distant parts of the body, such as the liver or lungs2,3. Five-year survival rates depend on stage and type of ovarian cancer with rates decreasing for advanced stage cancers that have spread to distant parts of the body3.

Precigen: Advancing Medicine with Precision
Precigen (Nasdaq: PGEN) is a dedicated discovery and clinical stage biopharmaceutical company advancing the next generation of gene and cell therapies using precision technology to target urgent and intractable diseases in our core therapeutic areas of immuno-oncology, autoimmune disorders, and infectious diseases. Our technologies enable us to find innovative solutions for affordable biotherapeutics in a controlled manner. Precigen operates as an innovation engine progressing a preclinical and clinical pipeline of well-differentiated unique therapies toward clinical proof-of-concept and commercialization. For more information about Precigen, visit www.precigen.com or follow us on Twitter @Precigen and LinkedIn.

Precigen’s UltraCAR-T Therapeutic Platform
Precigen’s UltraCAR-T platform has the potential to disrupt the CAR-T treatment landscape by increasing patient access through shortening manufacturing time, decreasing manufacturing-related costs, and improving outcomes using advanced approaches for precise tumor targeting and control of the immune system. The platform brings several key advancements: 1) Non-viral gene transfer using multigenic vectors for expression of multiple effector genes leads to better precision and control of tumor targeting and eliminates the need for virus; 2) Sustained persistence and desired phenotype of infused UltraCAR-T helps address T-cell exhaustion, a common issue with current CAR-T therapies; 3) T-cell control by incorporation of kill switch technology to potentially improve the safety profile; and 4) Rapid manufacturing of UltraCAR-T cells using our proprietary non-viral gene transfer process, which eliminates the need for ex vivo propagation, thus dramatically reducing wait times for patients from weeks to one day after gene transfer.

Trademarks
Precigen, UltraCAR-T, and Advancing Medicine with Precision are trademarks of Precigen and/or its affiliates. Other names may be trademarks of their respective owners.

On June 22, 2020 Silverback Therapeutics ("Silverback"), a biopharmaceutical company advancing a pipeline of therapies that are systemically delivered but locally active, reported that preclinical data for its lead ImmunoTAC candidate, SBT6050, will be presented at AACR (Free AACR Whitepaper) Virtual Annual Meeting 2020 Session II at 9:00 a.m. ET on June 22, 2020 (Press release, Silverback Therapeutics, JUN 22, 2020, View Source [SID1234561344]).

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The presentation, titled "SBT6050, a HER2-Directed TLR8 ImmunoTAC Therapeutic, is a Potent Human Myeloid Cell Agonist that Provides Opportunity for Single Agent Clinical Activity," shows that TLR8 agonism potently and uniquely activates human myeloid cells, driving a broad spectrum of anti-tumor immune mechanisms, including those not dependent on T cells.

In preclinical studies, SBT6050 activates human myeloid cells in the presence of HER2 expressing tumor cells, resulting in proinflammatory cytokine and chemokine production, inflammasome activation, and the indirect activation of cytolytic activity associated with T and NK cells. SBT6050’s functional profile was not replicated with conjugates comprised of TLR7-specific or resiquimod-derived agonists.

Robust, durable single agent activity is observed with the SBT6050 mouse surrogate in multiple tumor models, including those with low tumor infiltrating lymphocytes. In a human xenograft model lacking T, B, and NK cells, the SBT6050 mouse surrogate is curative as a single agent, demonstrating the ability of myeloid cells to mediate strong anti-tumor activity.

"TLR8’s robust expression and functional profile in human myeloid cells uniquely positions SBT6050 to potentiate anti-tumor responses through the activation of these innate immune cells present in tumors," said Valerie Odegard, Ph.D., Silverback’s chief scientific officer. "Our preclinical data highlight SBT6050’s potential to maximize anti-tumor immune responses, even in tumors lacking T cells. We are excited to be developing a much-needed immunotherapy for patients with HER2-expressing disease and will enter the clinic later this year."