On January 20, 2021 Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra), a clinical-stage biotechnology company focused on the development of novel therapies with the potential to improve the lives of patients with immune-mediated diseases, reported the closing of its underwritten public offering of 7,868,421 shares of its common stock at a public offering price of $9.50 per share, including 1,026,315 additional shares of common stock sold pursuant to the full exercise of the underwriters’ option to purchase additional shares (Press release, Aldeyra Therapeutics, JAN 20, 2021, View Source [SID1234574149]). All of the shares in the offering were sold by Aldeyra. The gross proceeds to Aldeyra following the underwriters’ exercise of their option to purchase additional shares, before deducting underwriting discounts and commissions and offering expenses, were approximately $74.7 million.

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Aldeyra anticipates using the net proceeds from the underwritten offering for the continued development of its lead compound, reproxalap, and its other product candidates, as well as for working capital, and other general corporate purposes.

Jefferies LLC and SVB Leerink LLC acted as joint book-running managers for the offering. BTIG LLC and Oppenheimer & Co. Inc. acted as co-lead managers for the offering.

The shares of common stock described above were offered by Aldeyra pursuant to a shelf registration statement on Form S-3 previously filed with the Securities and Exchange Commission (SEC) and declared effective by the SEC on July 27, 2018. A final prospectus supplement relating to and describing the terms of the offering was filed with the SEC on January 14, 2021, and is available on the SEC’s web site at www.sec.gov. Copies of the final prospectus supplement and accompanying prospectus relating to these securities may also be obtained by sending a request to: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, New York 10022, by telephone at 877-821-7388 or by email at [email protected], or from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, Massachusetts 02110, by telephone at 1-800-808-7525, ext. 6132, or by email at [email protected].

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

On January 20, 2021 AVEO Oncology (Nasdaq: AVEO) reported that it has received a commitment letter for an incremental $10 million loan from Hercules Capital, Inc. (NYSE: HTGC, "Hercules") and its affiliates, to be added to the current tranched, $35 million debt facility secured with Hercules in August 2020 through an amendment to the amended and restated loan and security agreement (the "Loan Agreement") (Press release, AVEO, JAN 20, 2021, View Source [SID1234574148]). Terms of the facility would remain otherwise unchanged from the Loan Agreement, with the loan bearing a maturity of 36 months, extendable up to 48 months, and an interest-only period of 12 months, extendable up to 30 months upon the achievement of performance milestones related to the approval and commercialization of tivozanib.

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Under the terms of the Loan Agreement, an initial tranche of $15 million was drawn down at signing. Under the terms of the commitment letter, a second tranche of $20 million would be available contingent upon the approval of the tivozanib New Drug Application ("NDA") by the U.S. Food and Drug Administration ("FDA") as a treatment for relapsed or refractory renal cell carcinoma ("RCC"). An additional $10 million will become available if certain sales criteria are met. As previously announced, the FDA has assigned AVEO’s NDA a Prescription Drug User Fee Act target action date of March 31, 2021. The nonbinding commitment letter is subject to AVEO and Hercules entering into a definitive amendment of the Loan Agreement setting forth the terms of the additional borrowing.

"The additional $10 million that would be made available from Hercules Capital with execution of a definitive amendment and the potential approval of tivozanib further supports what we believe will be a robust launch of tivozanib in the U.S.," said Michael Bailey, president and chief executive officer of AVEO. "As we work on expanding our commercial organization in preparation for this potential launch, we also continue to progress our pipeline of clinical programs, including our immunotherapy combination programs for tivozanib, our Phase 2 study of ficlatuzumab and our recently initiated Phase 1 study of AV-380. Throughout 2021, we look forward to a number of milestones designed to enhance our long-term value."

"We are pleased to be expanding our financing partnership with AVEO as they prepare for the potential approval and launch of tivozanib. This amendment and the potential further additional capital from Hercules represents another example of our unique ability to support innovative life sciences companies at all stages of development and through multiple value inflection points," said Bryan Jadot, Senior Managing Director and Life Sciences Group Head for Hercules.

On January 20, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a skin cancer diagnostics company providing personalized genomic information to improve cancer treatment decisions, reported poster presentations with data on two of its skin cancer gene expression profile tests at the 18th Annual Winter Clinical Dermatology Conference, taking place virtually from Jan. 15 – 24, 2021 (Press release, Castle Biosciences, JAN 20, 2021, View Source [SID1234574147]).

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President and chief executive officer, Derek Maetzold, will also participate in the meeting’s "2021 View for Dermatology Industry Panel," scheduled to take place on Saturday, Jan. 23, from 2:10 p.m. – 2:50 p.m. Eastern time.

Poster information is as follows:

DecisionDx-Melanoma:

The virtual poster is entitled, "Identifying predictors of sentinel lymph node metastasis in cutaneous melanoma patients using molecular and clinicopathologic high-risk features."

DecisionDx-Melanoma is Castle’s gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node (SLN) positivity, independent of traditional staging factors.

Study methods and findings:

For 3,093 patients with T1-T4 cutaneous melanoma, authors used decision tree analysis to determine which molecular and clinicopathologic features best stratify SLN positivity risk.
DecisionDx-Melanoma was the most important factor in distinguishing between high and low SLN-positivity rates (p<0.001).
DecisionDx DiffDx-Melanoma:

The virtual poster is entitled, "Performance of a 35-gene expression profile test in suspicious pigmented lesions of the head and neck."

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions.

"Melanomas of the head or neck need special consideration with respect to staging and treatment decisions, as many have inconclusive diagnoses upon presentation based on the histological and pathological factors normally used," said study author, Sarah I. Estrada, M.D., FCAP, laboratory director of Affiliated Dermatology. "We welcome the use of a gene expression profile test to help refine melanoma diagnoses of cases of indeterminate status. The study results demonstrate that DecisionDx DiffDx-Melanoma maintains its performance in this delicate sub-population of potential melanoma cases, and the utilization of this objective tool in clinical practice has the potential to improve subsequent management decisions."

Study methods and findings:

As melanoma of the head and neck often require special consideration with respect to staging and treatment decisions, early and accurate detection is especially critical for these lesions. This study evaluated DecisionDx DiffDx-Melanoma’s accuracy in classifying pigmented lesions on the head and neck.
DecisionDx DiffDx-Melanoma was used to independently assess 105 lesions located on the head and neck in adults age 18 and up.
DecisionDx DiffDx-Melanoma classified these lesions as benign (n=54, 51.4%), malignant (n=48, 45.7%), and intermediate-risk (n=3, 2.9%) with accuracy metrics of 98.0% sensitivity, 100% specificity, 100% PPV and 98.2% NPV.
The test’s performance in the head and neck lesion population is similar to its performance in pigmented lesions in the rest of the body in the overall adult population.
DecisionDx DiffDx-Melanoma demonstrated its ability to be an effective tool for refining melanoma diagnoses on the head and neck and therefore improving downstream management decisions, as indicated by its high sensitivity and specificity in this study.
About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Prediction of the likelihood of sentinel lymph node positivity has also been validated in two prospective multicenter studies that included more than 3,000 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results. Through September 30, 2020, DecisionDx-Melanoma has been ordered more than 64,560 times for use in patients with cutaneous melanoma.

More information about the test and disease can be found at www.CastleTestInfo.com.

About DecisionDx DiffDx-Melanoma

DecisionDx DiffDx-Melanoma is designed to aid dermatopathologists in characterizing difficult-to-diagnose melanocytic lesions. Of the approximately 2 million suspicious pigmented lesions biopsied annually in the U.S., Castle estimates that approximately 300,000 of those cannot be confidently classified as either benign or malignant through traditional histopathology methods. DecisionDx DiffDx-Melanoma classifies these lesions as: benign (gene expression profile suggestive of benign neoplasm); intermediate-risk (gene expression profile cannot exclude malignancy); or malignant (gene expression profile suggestive of melanoma). Interpreted in the context of other clinical, laboratory and histopathologic information, DecisionDx DiffDx-Melanoma is designed to add diagnostic clarity and confidence for dermatopathologists while helping dermatologists deliver more informed patient management plans.

On January 20, 2021 T-Cure Bioscience, Inc., a privately held clinical-stage immuno-oncology company developing the next generation of T cell receptor (TCR) therapies for patients with solid tumors, and Immunotech Biopharm Ltd ("Immunotech"), a leading cellular immunotherapy biopharmaceutical company focused on the research, development, and commercialization of T cell immunotherapies (HKEX: 6978), reported that they have entered into a license agreement for the research and development of T-Cure’s 800TCR product candidate, a HERV-E targeting TCR therapy for renal cell cancer (RCC), in China (Press release, T-Cure Bioscience, JAN 20, 2021, View Source [SID1234574146]). Under the terms of the agreement, Immunotech will make an upfront payment with T-Cure being eligible to receive additional future development milestone payments and tiered royalties on net sales of the product.

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T-Cure is currently developing 800TCR in the U.S. in collaboration with the National Heart Lung and Blood Institute (NHLBI), through a formal Collaborative Research and Development Agreement (CRADA). This TCR therapy is currently being evaluated in a Phase 1 trial at NHLBI for the treatment of metastatic clear cell Renal Cell Carcinoma (ccRCC) that failed an angiogenic inhibitor and a checkpoint inhibitor.

"We are extremely pleased to have entered into this agreement with Immunotech," stated Gang Zeng, Ph.D., Chief Executive Officer of T-Cure. "China represents a large opportunity for the 800TCR given the high prevalence of the haplotype, A11, which the TCR targets. With its advanced research, manufacturing, clinical operations, and marketing, Immunotech represents an ideal partner to help us advance the 800TCR in China."

"Our Company made a strong debut last year as the first pre-revenue cellular immunotherapy firm to trade on the Hong Kong Stock Exchange," added Dr. Wang Yu, Executive Director, CEO and co-CTO of Immunotech. "We see the addition of 800TCR as a natural expansion of our cell therapy product pipeline which currently consists of a number of product candidates. Moreover, the extensive experience of our management team with the research and clinical development of T cell immunotherapies will be extremely beneficial as we look to initiate clinical trials for 800TCR."

The HERV-E target is one of the quiescent Human Endogenous Retrovirus (HERV) sequences that are activated during tumor development. A growing number of HERV genes and proteins are expressed in different cancers raising the possibility that HERV derived antigens might represent excellent targets for tumor immunotherapy. HERV-E expression in renal cell carcinoma (RCC) is highly selective, with no transcripts detected in any normal tissues. In contrast to well-studied antigens such as NY-ESO-1 and MAGE, HERV-E represents a new frontier of TCR targets with significant clinical potential for immunotherapy.

On January 20, 2021 Merck KGaA, Darmstadt, Germany, a leading science and technology company, reported an update on the Phase III INTR@PID Lung 037 study and the extensive INTR@PID clinical trial program for the potential first-in-class investigational bifunctional immunotherapy bintrafusp alfa, in difficult-to-treat cancers, including biliary tract cancer (BTC) and cervical cancer (Praess release, Merck KGaA, JAN 20, 2021, View Source [SID1234574145]).

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The comprehensive INTR@PID program is designed to assess the impact of bintrafusp alfa across distinct cancers and settings where TGF-β is thought to play a driving role. TGF-β is a cytokine that is known to be associated with tumor propagation and metastatic potential such as local immunosuppression, fibrosis, growth of tumor blood vessels and chemo- or radiotherapy resistance through several mechanisms. Trapping TGF-β in the tumor microenvironment on top of PD-L1 blockade is thought to be transformative in different clinical settings.

While reviewing the totality of data from the ongoing clinical trial INTR@PID Lung 037 in the first-line treatment of patients with stage IV non-small cell lung cancer (NSCLC) that have high expression of PD-L1, the Independent Data Monitoring Committee recommended on January 19, 2021 to discontinue the clinical trial. Based on this recommendation, Merck KGaA, Darmstadt, Germany has made the decision to discontinue the clinical trial, as the study is unlikely to meet the co-primary endpoint, specifically progression-free survival. The recommendation by the Independent Data Monitoring Committee and the Company’s decision is related only to this clinical trial.

"We have pioneered the science behind bintrafusp alfa, and now through a strategic alliance, multiple non-correlated parallel hypotheses are being evaluated across numerous indications in our extensive INTR@PID clinical program," said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business of Merck KGaA, Darmstadt, Germany. "We remain committed to further evaluation of bintrafusp alfa, and these data from INTR@PID Lung 037 will provide important insights that may be applied to future studies."

Ongoing and New Clinical Trials

BTC: Topline results for the INTR@PID BTC 047 study are planned for Q1. Additionally,Phase II/III study of bintrafusp alfa in combination with chemotherapy as a first-line treatment for BTC (INTR@PID BTC 055), which is assessing a different hypothesis than the second-line monotherapy study, has completed enrollment in the Phase II portion and is on track for the Phase III portion. In 2020, the Japan Ministry of Health, Labour and Welfare granted SAKIGAKE ‘fast-track’ designation for bintrafusp alfa in BTC, a regulatory designation that enables an expedited review and is connected to indications with limited standards of care.
Cervical Cancer: The Phase II cervical cancer study (INTR@PID CERVICAL 017) initiated in 2020 is currently ongoing with enrollment nearing completion. The study is evaluating bintrafusp alfa for the treatment of patients with advanced, unresectable cervical cancer that progressed during or after platinum-containing chemotherapy. Human papillomavirus (HPV) infection has been closely associated with increased TGF-β expression in a variety of solid tumors, including cervical cancer.1 Encouraging efficacy of bintrafusp alfa in HPV-associated malignancies was reported from a pooled analysis of the Phase I (INTR@PID SOLID TUMOR 001) and a Phase II NCI-led trial.2 A new Phase I study in locally advanced/advanced cervical cancer as a combination therapy (INTR@PID CERVICAL 046) was also initiated in 2020.
NSCLC: The bintrafusp alfa lung program is designed to assess the patient population that may benefit from the dual mechanism of action focusing on combination studies (INTR@PID LUNG 005, INTR@PID LUNG 024). In addition to studying combinations with standards of care, the INTR@PID LUNG 024 study will expand to include new combinations, including combining with VEGF inhibitors, CTLA-4 targeted immunotherapies, and PARP inhibitors.
New Studies: Recently initiated monotherapy studies include a Phase II monotherapy study in patients with triple-negative breast cancer expressing high mobility group AT-hook 2 (HMGA2) (INTR@PID BREAST 020) and a Phase I monotherapy study in locally advanced/metastatic urothelial cancer (INTR@PID UROTHELIAL 152). A new Phase I multi-arm platform study combining bintrafusp alfa with GSK’s iCOS (feladilimab) is initiating.
*Bintrafusp alfa is currently under clinical investigation and not approved for any use anywhere in the world.

About Biliary Tract Cancer (BTC)
BTCs are a group of rare, aggressive gastrointestinal cancers associated with poor outcomes and limited treatment options. There is currently no globally accepted standard of care in the second-line setting and chemotherapy as well as immunotherapies have demonstrated low response rates in BTC. Epithelial-to-mesenchymal transition (EMT), a hallmark of tumor progression and drug resistance, plays an important role in BTC and has been shown to be triggered by TGF-β signaling.

About Cervical Cancer
The human papillomavirus (HPV) is responsible for more than 90 percent of cervical cancer cases and is one of the most common and deadliest cancers among women worldwide. The TGF-β pathway is frequently dysregulated in HPV-associated malignancies, including cervical cancer, and may contribute to development and progression of cervical cancer and generating resistance to immunotherapy. There is no globally accepted standard-of-care treatment for recurrent/metastatic cervical cancer after first-line systemic therapy.

About Non-small Cell Lung Cancer (NSCLC)
Non-small cell lung cancer remains one of the leading causes of cancer deaths worldwide with low five-year survival rates. There has been significant treatment progress with checkpoint inhibitors, but a majority of patients don’t respond.

About Bintrafusp Alfa
Bintrafusp alfa (M7824), discovered in-house at Merck KGaA, Darmstadt, Germany, and currently in clinical development through a strategic alliance with GSK, is a potential first-in-class investigational bifunctional fusion protein designed to simultaneously block two immunosuppressive pathways, TGF-β and PD-L1, within the tumor microenvironment. This bifunctional approach is thought to control tumor growth by potentially restoring and enhancing anti-tumor responses. In preclinical studies, bintrafusp alfa has demonstrated antitumor activity both as monotherapy and in combination with chemotherapy. Based on its mechanism of action, bintrafusp alfa offers a potential targeted approach to addressing the underlying pathophysiology of difficult-to-treat cancers.

About the INTR@PID Clinical Trial Program
INTR@PID is a global clinical trial program investigating the potential co-localized, dual inhibition of TGF-β and PD-L1 with bintrafusp alfa (M7824) in multiple tumor types. Current clinical trial information can be found on the INTR@PID website at www.intrapidclinicaltrials.com. To date, more than 1,300 patients with various types of solid tumors have been treated globally in the bintrafusp alfa INTR@PID clinical development program.

The INTR@PID clinical development strategy is comprehensive and is pursuing non-redundant hypotheses grounded in preclinical and early clinical data findings that continue to be explored and may yield clinically meaningful insights to patients in need, including exploring settings where simultaneous, synchronized targeting of TGF-β and PD-L1 may offer the key to expanding the potential of immunotherapy (lung cancer program); focusing on opportunities where PD-1/PD-L1 has suboptimal clinical activities and pathogenesis linked to TGF-β biology (studies in BTC and in urothelial cancers); and targeting specific tumors with biomarkers with a strong link to TGF-β signaling pathway (studies in TNBC and cervical cancer).

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