On March 22, 2021 EpimAb Biotherapeutics, a clinical stage biotech company specializing in bispecific antibody development, reported the closing of a $120 million Series C financing round (Press release, EpimAb Biotherapeutics, MAR 22, 2021, View Source [SID1234576974]). The round was co-led by China Merchants Bank International (CMBI) and Mirae Asset Financial Group (Mirae), and joined by Hony Capital, Cormorant Asset Management, Yanchuang Capital, Octagon Capital, renowned cultural entrepreneur and investor Adrian Cheng and ShangBay Capital, with strong participation from existing investors such as Decheng Capital, SDIC Fund, Sherpa Healthcare Partners, and Hidragon Capital. Proceeds from the financing will be used to fund the ongoing clinical development of EMB-01, EMB-02 and EMB-06, and to expand the company’s pipeline of novel bispecific antibodies and other biologics. Tony Rong, nominated by CMBI, and Sungwon Song, nominated by Mirae, will also join the EpimAb Board of Directors.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The completion of our Series C financing will enable us to accelerate the development of our three clinical assets EMB-01, EMB-02 and EMB-06, and to advance our rich pipeline of preclinical programs into the clinic as we continue to build on our portfolio of novel bispecific antibodies generated based on our proprietary FIT-Ig technology," said Dr. Chengbin Wu, founder and CEO of EpimAb Biotherapeutics. "With three candidates currently progressing through clinical trials and several ongoing high-value development projects in the pipeline poised to move towards the clinic, we are confident in our development strategy and our potential for long-term value generation. We greatly appreciate the support from our new and current investors as we move into this next phase of our company’s development and remain committed to bringing innovative bispecific antibody therapeutics to patients worldwide."

EpimAb is creating a pipeline of novel proprietary bispecific antibody therapeutics with a focus on oncology and other areas of high value to patients. EMB-01, EpimAb’s lead candidate designed to simultaneously target EGFR and cMET on tumor cells, is currently progressing through a Phase I/II clinical study in both China and the U.S. EMB-02, EpimAb’s second clinical candidate, which simultaneously targets two checkpoint proteins, PD-1 and LAG-3, and has shown strong anti-tumor activities in preclinical models resistant to standard anti-PD-1 monotherapies, recently received FDA clearance to progress into the clinic in the U.S. EMB-06, a T cell engaging bispecific designed to simultaneously target CD3 and BCMA with differentiated properties, has been cleared to initiate clinical trials in Australia.

"EpimAb is among the premier innovative biopharmaceutical companies in China, revolutionizing the bispecific antibody space with a proprietary technology that has global potential," said Tony Rong. "As we continue to expand our global life sciences portfolio, CMBI is committed to support EpimAb’s mission of bringing novel bispecific therapeutics to patients."

"Each of EpimAb’s assets impressed us with enormous potential and a unique approach to treating areas of high unmet medical need. EpimAb’s dedicated pipeline of bispecific antibodies with best-in-class mechanisms makes it one of the driving forces behind Chinese biopharma innovations," said Sungwon Song. "Mirae is excited to be a part of the company’s rapid evolution to become a global leader in its space."

On March 22, 2021 Scholar Rock (NASDAQ: SRRK), a clinical-stage biopharmaceutical company focused on the treatment of serious diseases in which protein growth factors play a fundamental role, reported the publication of preclinical development data for SRK-181 in the peer-reviewed journal International Journal of Toxicology (Press release, Scholar Rock, MAR 22, 2021, View Source [SID1234576973]). SRK-181 is a product candidate that has been shown to be a potent and highly specific inhibitor of latent growth factor-beta 1 (TGFβ1) activation in preclinical studies. SRK-181 is being developed to overcome primary resistance to checkpoint inhibitor therapy and is currently being studied in the two-part DRAGON Phase 1 trial in patients with locally advanced or metastatic solid tumors exhibiting primary resistance to anti-PD-(L)1 therapy.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This publication provides a comprehensive preclinical assessment of the pharmacology, pharmacokinetics, and safety of SRK-181, which support its evaluation in the DRAGON Phase 1 trial," said Gregory Carven, Ph.D., Chief Scientific Officer of Scholar Rock. "The initial clinical response and safety data from the DRAGON trial, which we anticipate by end of year, will provide an early look into SRK-181’s safety and tolerability profile and the potential for a specific inhibitor of latent TGFβ1 to overcome the immune exclusion that we believe, for many patients, is responsible for primary resistance to checkpoint inhibitor therapies."

Targeting the TGFβ1 Pathway

Greater understanding of the role of TGFβ signaling in promoting cancer progression has led to heightened interest in the development of therapies that inhibit the TGFβ pathway. However, most of the approaches to date have been non-selective and target at least two of the three TGFβ isoforms, which may limit the therapeutic window and potentially result in a lack of efficacy, an unfavorable safety profile, or a combination of the two. Examples of dose-limiting toxicities observed nonclinically for nonselective anti-TGFβ therapies include cardiovascular abnormalities, skin lesions, epithelial oral hyperplasia, and gingival bleeding.

Scholar Rock’s approach to targeting the TGFβ pathway is fundamentally different. SRK-181 is a highly specific inhibitor of the latent TGFβ1 isoform with minimal or no binding to latent TGFβ2, latent TGFβ3, or any of the active TGFβ growth factors based on in vitro studies. Based on preclinical evaluations of SRK-181’s pharmacologic and safety profiles across multiple animal species, SRK-181 may offer an improved safety profile and a wider therapeutic window than non-selective TGFβ inhibitors.

About the Preclinical Data

The International Journal of Toxicology publication, "Nonclinical Development of SRK-181: An Anti-latent TGFβ1 Monoclonal Antibody for the Treatment of Locally Advanced or Metastatic Solid Tumors," provides a comprehensive preclinical assessment of the pharmacology, pharmacokinetics, and safety of SRK-181. (Welsh et al., Int J. Tox, March 19, 2021). Key findings include:

Selective inhibition of latent TGFβ1 activation by SRK-181 was shown to avoid dose-limiting toxicities associated with pan-TGFβ inhibitors in preclinical pharmacology studies.
In-vitro studies showed that SRK-181 had no effect on human platelet aggregation, activation, or binding and that SRK-181 does not trigger a proinflammatory cytokine response in peripheral blood mononuclear cells (PBMC).
Four-week toxicology study showed that weekly intravenous administration of SRK-181 achieved sustained serum exposure and was well-tolerated in rats and monkeys with no treatment-related adverse findings.
No observed adverse effect level (NOAEL) of 200 mg/kg and 300 mg/kg were achieved in rats and cynomolgus monkeys, respectively.
Preclinical pharmacologic and pharmacokinetics assessments provided support for the dose-selection strategy for the ongoing DRAGON Phase 1 trial in patients with solid tumors.
About SRK-181

SRK-181 is a selective inhibitor of TGFβ1 activation and is an investigational product candidate being developed to overcome primary resistance to checkpoint inhibitor therapy, such as anti-PD-(L)1 antibodies. TGFβ1 is the predominant TGFβ isoform expressed in many human tumors, particularly for those tumors where checkpoint therapies are currently approved. Based on profiling of human tumors that are resistant to anti-PD-(L)1 therapy, data suggests TGFβ1 is a key contributor to excluding immune cell entry into the tumor microenvironment, thereby preventing normal immune function. Scholar Rock believes SRK-181 has the potential to overcome this immune cell exclusion and induce tumor regression when administered in combination with anti-PD-(L)1 therapy. By specifically targeting the latent TGFβ1 isoform, Scholar Rock hypothesizes that SRK-181 can increase the therapeutic window by potentially avoiding toxicities associated with non-selective TGFβ inhibition. A Phase 1 proof-of-concept clinical trial in patients with locally advanced or metastatic solid tumors is ongoing. The effectiveness and safety of SRK-181 have not been established and SRK-181 has not been approved for any use by the FDA or any other regulatory agency.

On March 22, 2021 AVEO Oncology (Nasdaq: AVEO) reported that it has commenced an underwritten public offering of 5,000,000 shares of its common stock. In connection with the offering, AVEO intends to grant the underwriters a 30-day option to purchase up to an additional 750,000 shares of its common stock (Press release, AVEO, MAR 22, 2021, View Source [SID1234576972]). All of the shares in the offering are to be sold by AVEO. The offering is subject to market and other conditions, and there can be no assurance as to whether or when the offering may be completed, or as to the actual size or terms of the offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The net proceeds of the offering are expected to be used for working capital and general corporate purposes, including to support commercialization activities relating to FOTIVDA (tivozanib) and to advance AVEO’s pipeline.

SVB Leerink and Stifel are acting as joint bookrunning managers for the offering.

The shares are being offered by AVEO pursuant to a shelf registration statement on Form S-3 that was filed with the Securities and Exchange Commission ("SEC") on November 9, 2020 and declared effective by the SEC on November 18, 2020. A preliminary prospectus supplement 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 www.sec.gov.

Copies of the preliminary prospectus supplement and the accompanying prospectus relating to this offering can be obtained from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at (800) 808-7525, ext. 6105 or by email at [email protected]; or Stifel, Nicolaus & Company, Incorporated, Attention: Syndicate, One Montgomery Street, Suite 3700, San Francisco, CA 94104, by telephone at (415) 364-2720 or by email at [email protected]. The final terms of the offering will be disclosed in a final prospectus supplement to be filed with the SEC.

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

On March 22, 2021 Lantheus Holdings, Inc. (NASDAQ: LNTH) (Lantheus), an established leader and fully integrated provider of innovative imaging diagnostics, targeted therapeutics and artificial intelligence solutions to find, fight and follow serious medical conditions, reported that updated biochemical tumor marker data from its pivotal Phase 2 trial of AZEDRA (iobenguane I 131) were presented at the Endocrine Society’s 2021 Annual Meeting, ENDO 2021 (Press release, Lantheus Medical Imaging, MAR 22, 2021, View Source [SID1234576971]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Dr. Camilo Jimenez, Professor of Endocrine Neoplasia and Hormonal Disorders at the University of Texas MD Anderson Cancer Center, delivered an oral presentation entitled: "Biochemical Tumor Marker Status and Its Role in Treatment Response in Patients Who Received High-Specific-Activity I-131 MIBG in Advanced Pheochromocytoma and Paraganglioma (PPGL): Results from a Pivotal Phase 2 Clinical Trial" on Saturday, March 20, 2021.

"AZEDRA yielded reductions in hypersecreted tumor biomarkers in a majority of patients in this pivotal study of advanced pheochromocytoma and paraganglioma," said Dr. Jimenez. "In addition, the overall tumor biomarker response correlated significantly with both the primary and secondary endpoint responses in the study, underscoring the clinical utility and relevance of this important biochemical endpoint to the therapeutic benefit of AZEDRA in patients with these life-threatening tumors."

Tumor biomarkers were analyzed in patients with hypersecreting tumors (tumor biomarkers 1.5x above the upper limit of normal at baseline). The best biochemical responses (complete response (CR) or partial response (PR) at any time after treatment as evidenced by significant biomarker reductions) were observed in 80% (Chromogranin A), 70% (total metanephrines) and 64% (vanillylmandelic acid) of patients administered at least one therapeutic dose of AZEDRA. The overall tumor biomarker response correlated significantly with the best confirmed objective tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 (including PR and stable disease; r=0.35, p=0.006). Importantly, none of the responders with an overall biomarker response (CR or PR) had progressive disease as best response per RECIST.

"AZEDRA is the first and only approved treatment option for patients with advanced or metastatic PPGL," said Istvan Molnar, M.D., Chief Medical Officer of Lantheus. "Elevated neuroendocrine markers are the hallmark of these diseases and are responsible for many of the signs and symptoms of PPGL. We believe these data support the established efficacy of AZEDRA in its approved indication by demonstrating that after treatment with AZEDRA, the majority of patients with elevated baseline neuroendocrine markers had a reduction of these markers."

Indication

AZEDRA (iobenguane I 131) is indicated for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.

Important Safety Information

Warnings and Precautions:

Risk from radiation exposure: AZEDRA contributes to a patient’s overall long-term radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. These risks of radiation associated with the use of AZEDRA are greater in pediatric patients than in adults. Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment with AZEDRA consistent with institutional good radiation safety practices and patient management procedures.

Myelosuppression: Severe and prolonged myelosuppression occurred during treatment with AZEDRA. Among the 88 patients who received a therapeutic dose of AZEDRA, 33% experienced Grade 4 thrombocytopenia, 16% experienced Grade 4 neutropenia, and 7% experienced Grade 4 anemia. Five percent of patients experienced febrile neutropenia. Monitor blood cell counts weekly for up to 12 weeks or until levels return to baseline or the normal range. Withhold and dose reduce AZEDRA as recommended in the prescribing information based on severity of the cytopenia.

Secondary myelodysplastic syndrome, leukemia, and other malignancies: Myelodysplastic syndrome (MDS) and acute leukemias were reported in 6.8% of the 88 patients who received a therapeutic dose of AZEDRA. The time to development of MDS or acute leukemia ranged from 12 months to 7 years. Two of the 88 patients developed a non-hematological malignancy.

Hypothyroidism: Hypothyroidism was reported in 3.4% of the 88 patients who received a therapeutic dose of AZEDRA. Initiate thyroid-blocking medications starting at least 1 day before and continuing for 10 days after each AZEDRA dose to reduce the risk of hypothyroidism or thyroid neoplasia. Evaluate for clinical evidence of hypothyroidism and measure thyroid-stimulating hormone (TSH) levels prior to initiating AZEDRA and annually thereafter.

Elevations in blood pressure: Eleven percent of the 88 patients who received a therapeutic dose of AZEDRA experienced a worsening of pre-existing hypertension defined as an increase in systolic blood pressure to ≥160 mmHg with an increase of 20 mmHg or an increase in diastolic blood pressure to ≥100 mmHg with an increase of 10 mmHg. All changes in blood pressure occurred within the first 24 hours post infusion. Monitor blood pressure frequently during the first 24 hours after each therapeutic dose of AZEDRA.

Renal toxicity: Of the 88 patients who received a therapeutic dose of AZEDRA, 7% developed renal failure or acute kidney injury and 22% demonstrated a clinically significant decrease in glomerular filtration rate (GFR) measured at 6 or 12 months. Monitor renal function during and after treatment with AZEDRA. Patients with baseline renal impairment may be at greater risk of toxicity; perform more frequent assessments of renal function in patients with mild or moderate impairment. AZEDRA has not been studied in patients with severe renal impairment.

Pneumonitis: Fatal pneumonitis occurred 9 weeks after a single dose in one patient in the expanded access program. Monitor patients for signs and symptoms of pneumonitis and treat appropriately.

Embryo-fetal toxicity: Based on its mechanism of action, AZEDRA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating AZEDRA. Advise females and males of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with AZEDRA and for 7 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the final dose.

Risk of infertility: Radiation exposure associated with AZEDRA may cause infertility in males and females. Radiation absorbed by testes and ovaries from the recommended cumulative dose of AZEDRA is within the range where temporary or permanent infertility can be expected following external beam radiotherapy.

Adverse Reactions: The most common severe (Grade 3–4) adverse reactions observed in AZEDRA clinical trials (≥10%) were lymphopenia (78%), neutropenia (59%), thrombocytopenia (50%), fatigue (26%), anemia (24%), increased international normalized ratio (18%), nausea (16%), dizziness (13%), hypertension (11%), and vomiting (10%). Twelve percent of patients discontinued treatment due to adverse reactions (thrombocytopenia, anemia, lymphopenia, nausea and vomiting, multiple hematologic adverse reactions).

Drug Interactions: Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells and therefore interfere with dosimetry calculations or the efficacy of AZEDRA. These drugs were not permitted in clinical trials that assessed the safety and efficacy of AZEDRA. Discontinue the drugs listed in the prescribing information for at least 5 half-lives before administration of either the dosimetry dose or a therapeutic dose of AZEDRA. Do not administer these drugs until at least 7 days after each AZEDRA dose.

On March 22, 2021 Aura Biosciences, a clinical-stage oncology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the closing of an oversubscribed $80 million financing (Press release, Aura Biosciences, MAR 22, 2021, View Source [SID1234576969]). The financing was led by Matrix Capital Management and Surveyor Capital (a Citadel company) with participation from new investors, including Rock Springs Capital, Adage Capital Management LP and Velosity Capital. Existing investors Medicxi, Advent Life Sciences, Lundbeckfonden Ventures, Arix Bioscience, Chiesi Ventures, Ysios Capital and Columbus Venture Partners also participated in the round.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Aura intends to use the proceeds from this financing to advance the clinical development of its VDC technology platform, including the pivotal Phase 3 program for AU-011, the Company’s lead candidate in development for the first line treatment of choroidal melanoma, and ongoing research for additional programs in ocular oncology, as well as expanding the VDC technology into bladder cancer, the first non-ophthalmic solid tumor indication.

"Aura is pioneering the development of a new class of targeted therapies for life-threatening cancers with our novel VDC technology platform. This funding from a syndicate of distinguished investors enables us to advance AU-011 into a pivotal Phase 3 program for the first line treatment of choroidal melanoma, a rare, life- and vision-threatening form of cancer with no drugs approved. It also allows us to continue to expand the reach of our VDC technology in additional ocular oncology indications and in the treatment of solid tumors like bladder cancer where there is a high unmet medical need for better targeted therapies to treat early and reduce the incidence of metastasis," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura.

In connection with this financing, Karan Takhar, Senior Managing Director of Matrix Capital Management, will join Aura’s Board of Directors.

Mr. Takhar said, "Matrix believes in the long-term potential of Aura’s VDC technology to further strengthen the Company’s position as a leader in ocular oncology and beyond within other types of cancers in need of better treatment options. We look forward to supporting Aura’s leadership team through this next stage of pipeline growth and transition into late-stage development with the commencement of the AU-011 pivotal program."

About AU-011 (belzupacap sarotalocan)

AU-011 is a first-in-class virus-like drug conjugate (VDC) therapy in development for the first line treatment of choroidal melanoma. The virus-like component of the VDC selectively binds unique heparan sulphate proteoglycans (HSPGs) that are modified and overexpressed on the tumor cell surface of choroidal melanoma cells (and other tumors) and delivers a potent cytotoxic drug that is activated with infrared light. Upon activation with an ophthalmic laser, the cytotoxic drug rapidly and specifically disrupts the cell membrane of malignant melanoma cells with a pro-immunogenic cell death that is believed to activate the immune system generating long term anti-tumor immunity. The unique specificity of tumor binding by the VDC enables the preservation of key eye structures, which may allow for the potential of preserving patients’ vision and reducing other long-term complications of radiation treatment. The possibility of early treatment intervention and the activation of the immune system could lead to a reduction in the metastatic rate for patients with this life-threatening disease. AU-011 can be delivered using equipment commonly found in an ophthalmologist’s office and does not require a surgical procedure, pointing to a potentially less invasive, more convenient therapy for patients and physicians. AU-011 for the treatment of choroidal melanoma has been granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration and is currently in Phase 2 clinical development.