On August 8, 2018 Apexigen, Inc., a clinical-stage biopharmaceutical company, reported the successful completion of its Series B and Series C financings in which it raised a total of $73 million (Press release, Apexigen, AUG 8, 2018, View Source [SID1234528533]).

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The $15 million Series B financing was led by Decheng Capital and the recent $58 million Series C financing was led by 3E Bioventures Capital, Virtus Inspire Ventures, and SV Tech Ventures. As a result of these financings, Apexigen’s Board of Directors was expanded to include Dan Zabrowski, Ph.D. of Decheng Capital, and Karen Liu, Ph.D. of 3E Bioventures Capital.

Apexigen intends to use these proceeds to advance the clinical development of its lead immuno-oncology (I-O) therapeutic APX005M, a monoclonal antibody targeting CD40. Currently, APX005M is in multiple Phase 2 clinical trials to treat different types of cancers. The proceeds will also be used to discover and develop Apexigen’s broader pipeline of therapies.

"Completing these financings puts Apexigen on a new trajectory for growth. We now have the resources to both execute our clinical development strategy for APX005M and accelerate building our pipeline of novel therapeutics based on our proprietary product discovery platform APXiMAB", said Xiaodong Yang, M.D., Ph.D., President and Chief Executive Officer of Apexigen. "For APX005M, we are conducting a robust clinical program with 8 ongoing clinical trials, as we believe CD40 activation by APX005M will become a key component in several new I-O therapeutic regimens for treating cancer patients. Looking ahead, we will use our powerful discovery research engine to accelerate generation of new I-O therapeutics."

About APX005M
APX005M is a novel, humanized monoclonal antibody that stimulates the anti-tumor immune response. APX005M targets CD40, a co-stimulatory receptor that is essential for activating both innate and adaptive immune systems. Binding of APX005M to CD40 on antigen presenting cells (i.e., dendritic cells, monocytes and B-cells) initiates a multi-faceted immune response bringing multiple components of the immune system (e.g., T cells, macrophages) to work in concert against cancer. APX005M is currently in Phase 2 clinical development for the treatment of cancers such as melanoma, non-small cell lung cancer, pancreatic cancer and renal cell carcinoma in various combinations with immunotherapy, chemotherapy or radiation therapy.

On August 8, 2018 Synthetic Biologics, Inc. (NYSE American: SYN), a late-stage clinical company developing therapeutics that preserve the microbiome to protect and restore the health of patients, reported financial results for the three months ended June 30, 2018 (Press release, Synthetic Biologics, AUG 8, 2018, View Source [SID1234528532]).

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"Following several productive meetings earlier this year, we are pleased to have reached preliminary agreement on key elements of our planned Phase 3 clinical trial for ribaxamase, our first-in-class therapeutic intervention designed to prevent the onset of primary C. difficile infection (CDI) by protecting the gut microbiome from antibiotic-mediated dysbiosis. We are in the process of optimizing a protocol synopsis for the Phase 3 clinical trial which we will discuss with the FDA at our end of Phase 2 meeting which is currently planned to take place towards the end of the third quarter," stated Steven A. Shallcross, Interim Chief Executive Officer and Chief Financial Officer.

"We will continue to work closely and collaboratively with the FDA to define a clear and achievable pathway toward gaining marketing approvals. In our ongoing interactions with FDA, what has become clear is their recognition of the unmet need for novel interventions to combat and prevent the proliferation of CDI. With more than 450,000 cases of CDI each year in the U.S., if approved, ribaxamase will be the first intervention specifically designed to prevent CDI associated with the most commonly used IV antibiotics," concluded Shallcross.

Clinical Development and Operational Update

Announced the Company reached preliminary agreement with the FDA on key elements of a proposed Phase 3 clinical program for SYN-004 (ribaxamase), which is expected to:
Comprise a global, event driven clinical trial with a fixed maximum number of patients for total enrollment,
Evaluate the potential efficacy and safety of ribaxamase in a broader patient population by the inclusion of additional IV β-lactam antibiotics in addition to ceftriaxone and by enrolling patients with a variety of underlying infections,
Evaluate the ability of ribaxamase to reduce the incidence of Clostridium difficile infection (CDI) in the ribaxamase treatment group compared to placebo as the primary efficacy endpoint,
Evaluate mortality risk as the co-primary safety endpoint which will be separate from the primary efficacy endpoint of reduction in the incidence of CDI,
Anticipate End-of-Phase 2 meeting with the FDA in 3Q 2018 to solidify the remaining elements of the planned SYN-004 (ribaxamase) Phase 3 clinical trial;
Plan to initiate SYN-004 (ribaxamase) Phase 3 clinical trial in 2H 2019;
Continue efforts to solidify clinical infrastructure, including exploring international regulatory and market access structures to support advancement of SYN-010, designed to treat an underlying cause of the symptoms associated with irritable bowel syndrome with constipation (IBS-C);
Reported supportive data from a second canine animal model demonstrating that when co-administered with oral amoxicillin and oral Augmentin, oral SYN-007 did not interfere with systemic absorption of the antibiotics but did diminish microbiome damage associated with these antibiotics in 2Q 2018.
Quarter Ended June 30, 2018 Financial Results

General and administrative expenses decreased by 13% to $1.4 million for the three months ended June 30, 2018, compared to $1.6 million for the same period in 2017. This decrease is primarily the result of lower salary expense, stock compensation, and related benefits costs incurred during the three months ended June 30, 2018 as compared to the three months ended June 30, 2017 due to the resignation of the Chief Executive Officer, along with the reduction of travel and consulting expense, offset by higher registration, investor relations and legal costs. The charge related to stock-based compensation expense was $264,000 for the three months ended June 30, 2018, compared to $539,000 for three months ended June 30, 2017.

Research and development expenses decreased by 25% to $3.6 million for the three months ended June 30, 2018, from $4.8 million for the three months ended June 30, 2017. This decrease is primarily the result of lower SYN-004 (ribaxamase) and SYN-010 program costs for 2018 since no clinical trials were ongoing during the quarter. The research and development costs incurred during the quarter were primarily related to planning for future Phase 3 (SYN-004) and Phase 2b/3 (SYN-010) clinical programs as we seek to secure the financial resources necessary for the completion of these clinical trials. The charge related to stock-based compensation expense was $293,000 for the three months ended June 30, 2018, compared to $331,000 for the same period in 2017.

Other income was $789,000 million for the three months ended June 30, 2018, compared to other income of $2.2 million for the same period in 2017. Other income for the three months ended June 30, 2018 is primarily comprised of non-cash income of $783,000 million from the change in fair value of warrants. The decrease in the fair value of the warrants was due to the decrease in our stock price from the prior quarter.

Cash and cash equivalents as of June 30, 2018 was $7.1 million, a decrease of $10.0 million from December 31, 2017.

Conference Call

Synthetic Biologics will hold a conference call today, Wednesday, August 8, 2018, at 4:30 p.m. (EDT). The dial-in information for the call is as follows, U.S. toll free: +1 888-347-5280 or International: +1 412-902-4280. Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archive of the call will be available for replay at the same URL, View Source, for 90 days after the call.

On August 8, 2018 Clovis Oncology, Inc. (NASDAQ: CLVS) reported the randomization of the first patient in the Phase 3 ATHENA trial evaluating the combination of Clovis’ Rubraca(rucaparib), a poly (ADP ribose) polymerase inhibitor (PARP), and Bristol-Myers Squibb’s PD-1 inhibitor, OPDIVO (nivolumab), for the treatment of advanced ovarian cancer (Press release, Clovis Oncology, AUG 8, 2018, View Source [SID1234528526]). ATHENA, sponsored by Clovis, is part of a clinical collaboration with Bristol-Myers Squibb and is being conducted in association with the Gynecologic Oncology Group (GOG) and the European Network for Gynecological Oncological Trials (ENGOT). GOG and ENGOT are the two largest cooperative groups in the U.S. and Europe dedicated to the treatment of gynecological cancers.

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"I am pleased the GOG and ENGOT are conducting the first trial designed to investigate whether the combination of a PARP inhibitor and PD-1 blocking antibody can demonstrate not only an improvement in progression-free survival in the first-line maintenance setting for women with advanced ovarian cancer, but also whether the combination can change the natural course of the disease by delaying or reducing recurrence following front-line therapy," said Brad Monk, M.D., FACS, FACOG, Arizona Oncology (US Oncology Network), Professor, Gynecologic Oncology at University of Arizona and Creighton University, Medical Director of US Oncology Research Gynecology program in Phoenix, Arizona and Lead Investigator of the ATHENA trial.

"Rubraca combination trials such as ATHENA are encouraging to see, because the possible implications are particularly meaningful for women with advanced ovarian cancer, who need a wide range of treatment options," said Dr. Rebecca Kristeleit, Clinical Senior Lecturer and Consultant Medical Oncologist, University College London, U.K. and ATHENA ENGOT/Non-U.S. Lead Investigator. "The participation by the GOG and the ENGOT in the evaluation of a PARP inhibitor in combination with a PD-1 agent reflects the interest around this approach."

ATHENA is a Phase 3, randomized, multinational, double-blind, placebo-controlled, four-arm trial evaluating Rubraca and Opdivo as maintenance treatment following response to front-line treatment in newly-diagnosed ovarian cancer patients. Response to treatment will be analyzed based on homologous recombination (HR) status of tumor samples. The primary endpoint is investigator assessed progression-free survival (PFS); secondary endpoints include overall survival (OS), objective response rate (ORR), duration of response (DOR), and safety.

"The initiation of the Phase 3 ATHENA trial is an important milestone for Clovis and a critical step towards helping women with advanced ovarian cancer, who are in need of new treatment options. We are particularly excited about the potential clinical utility of Rubraca in combination with Opdivo in this setting," said Patrick J. Mahaffy, President and Chief Executive Officer of Clovis Oncology. "The importance of this trial is also underscored by the participation of ENGOT and GOG, which we anticipate may facilitate enrollment."

The trial will enroll approximately 1,000 ovarian cancer patients at clinical trial centers in the United States and internationally. More information about the trial is available at www.clinicaltrials.gov, identifier NCT03522246.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in multiple tumor types, including ovarian, metastatic castration-resistant prostate, and bladder cancers, as monotherapy, and in combination with other anti-cancer agents. Exploratory studies in other tumor types are also underway. Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed medical product outside of the U.S. and Europe.

Rubraca EU Authorized Use

Rubraca is licensed for adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy.

Click here to access the current Summary of Product Characteristics. Healthcare professionals should report any suspected adverse reactions via their national reporting systems.

Rubraca U.S. FDA Approved Indications and Important Safety Information

Rubraca is indicated as monotherapy for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

Rubraca is indicated as monotherapy for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

Select Important Safety Information

Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur uncommonly in patients treated with Rubraca, and are potentially fatal adverse reactions. In approximately 1,100 treated patients, MDS/AML occurred in 12 patients (1.1%), including those in long term follow-up. Of these, 5 occurred during treatment or during the 28-day safety follow-up (0.5%). The duration of Rubraca treatment prior to the diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The cases were typical of secondary MDS/cancer therapy-related AML; in all cases, patients had received previous platinum-containing regimens and/or other DNA damaging agents. Do not start Rubraca until patients have recovered from hematological toxicity caused by previous chemotherapy (≤ Grade 1).

Monitor complete blood counts for cytopenia at baseline and monthly thereafter for clinically significant changes during treatment. For prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or reduce dose (see Dosage and Administration (2.2) in full Prescribing Information) and monitor blood counts weekly until recovery. If the levels have not recovered to Grade 1 or less after 4 weeks or if MDS/AML is suspected, refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue Rubraca.

Based on its mechanism of action and findings from animal studies, Rubraca can cause fetal harm when administered to a pregnant woman. Apprise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of Rubraca.

Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1-4) were nausea (76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash (43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%), constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia (29%), nasopharyngitis/upper respiratory tract infection (29%), stomatitis (28%), decreased appetite (23%), and neutropenia (20%).

Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1-4) were increase in creatinine (98%), decrease in hemoglobin (88%), increase in cholesterol (84%), increase in alanine aminotransferase (ALT) (73%), increase in aspartate aminotransferase (AST) (61%), decrease in platelets (44%), decrease in leukocytes (44%), decrease in neutrophils (38%), increase in alkaline phosphatase (37%), and decrease in lymphocytes (29%).

Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1-4) were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%), constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea (34%), abdominal pain (32%), dyspnea (21%), and thrombocytopenia (21%).

Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%; Grade 1-4) were increase in creatinine (92%), increase in alanine aminotransferase (ALT) (74%), increase in aspartate aminotransferase (AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes (45%), increase in cholesterol (40%), decrease in platelets (39%), and decrease in absolute neutrophil count (35%).

Co-administration of Rubraca can increase the systemic exposure of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, if clinically indicated. If co-administration with warfarin (a CYP2C9 substrate) cannot be avoided, consider increasing frequency of international normalized ratio (INR) monitoring. Because of the potential for serious adverse reactions in breast-fed children from Rubraca, advise lactating women not to breastfeed during treatment with Rubraca and for 2 weeks after the last dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Clovis Oncology, Inc. at 1-844-258-7662.

On August 8, 2018 Heron Therapeutics, Inc. (Nasdaq: HRTX), a commercial-stage biotechnology company focused on improving the lives of patients by developing best-in-class treatments to address some of the most important unmet patient needs, today reported financial results for the three and six months ended June 30, 2018 and highlighted recent corporate progress.

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Recent Corporate Progress

Pain Management Franchise

Positive Topline Results from Phase 2b Clinical Studies of HTX-011 in Total Knee Arthroplasty and Breast Augmentation. HTX-011 achieved all primary endpoints in two completed Phase 2b studies: Study 209 (local administration in total knee arthroplasty) and Study 211 (instillation or pectoral pocket nerve block in breast augmentation). In both of these studies:
HTX-011 demonstrated statistically significant reductions in both pain intensity and opioid use;
HTX-011 demonstrated a strong correlation between pain reduction and pharmacokinetics; and
HTX-011 was well tolerated.
Breakthrough Therapy Designation Granted for HTX-011. The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for HTX-011 for local administration into the surgical site. Breakthrough Therapy designation is designed to expedite the development and review of drugs that are intended to treat serious conditions and for which preliminary clinical evidence indicates substantial improvement over available therapies on clinically significant endpoint(s). Breakthrough Therapy designation was granted for HTX-011 based on the results of completed Phase 2 studies and two recently completed Phase 3 studies, which showed that HTX-011 produced significant reductions in both pain intensity and the need for opioids through 72 hours post-surgery compared to placebo and bupivacaine solution, the standard of care.
In the second half of 2018, Heron expects to submit a New Drug Application (NDA) to the FDA for HTX-011.

CINV Franchise

CINV Sales. Chemotherapy-induced nausea and vomiting (CINV) franchise net product sales for the three and six months ended June 30, 2018 were $17.3 million and $28.8 million, respectively. Heron reaffirms full-year 2018 CINV franchise net product sales guidance of $60 million to $70 million, and Heron believes net product sales will be in the upper end of this range.
SUSTOL Sales. Net product sales of SUSTOL (granisetron) extended-release injection for the three and six months ended June 30, 2018 were $6.1 million and $12.4 million, respectively. The entry of generic palonosetron in the first quarter of 2018 has had, and is expected to have, a several-quarter negative impact on provider demand for SUSTOL.
CINVANTI Sales. Net product sales of CINVANTI (aprepitant) injectable emulsion for the three and six months ended June 30, 2018 were $11.2 million and $16.4 million, respectively. CINVANTI was approved by the FDA on November 9, 2017 and became commercially available in the U.S. on January 4, 2018.
"We are pleased with the progress we have made in the first half of 2018. In our pain management franchise, the results of completed Phase 2 and Phase 3 studies and the Breakthrough Therapy designation by the FDA of HTX-011 further confirm our belief in the superiority of HTX-011 over the standard of care in reducing pain intensity and opioid use across multiple diverse surgical models. In our CINV franchise, providers are continuing to realize the value of CINVANTI over other injectable NK1 receptor antagonists, and the number of oncology clinics ordering CINVANTI has increased," said Barry D. Quart, Pharm.D., Chief Executive Officer of Heron Therapeutics. "We look forward to submitting an NDA for HTX-011 to the FDA in the second half of this year and achieving full-year CINV net product sales in the upper end of our $60 million to $70 million guidance."

Financial Results

Net product sales for the three and six months ended June 30, 2018 were $17.3 million and $28.8 million, respectively, compared to $8.5 million and $12.1 million for the same periods in 2017, respectively.

Heron’s net loss for the three and six months ended June 30, 2018 was $38.7 million and $90.9 million, or $0.54 per share and $1.33 per share, respectively, compared to $42.8 million and $93.1 million, or $0.80 per share and $1.79 per share, for the same periods in 2017, respectively. Net loss for the three and six months ended June 30, 2018, included non-cash, stock-based compensation expense of $7.8 million and $15.5 million, respectively, compared to $8.2 million and $16.2 million, for the same periods in 2017, respectively.

As of June 30, 2018, Heron had cash, cash equivalents and short-term investments of $423.0 million, compared to $172.4 million as of December 31, 2017. Net cash used for operating activities for the six months ended June 30, 2018 was $122.4 million, compared to $82.6 million for the same period in 2017.

About HTX-011 for Postoperative Pain

HTX-011, which utilizes Heron’s proprietary Biochronomer drug delivery technology, is an investigational, long-acting, extended-release formulation of the local anesthetic bupivacaine in a fixed-dose combination with the anti-inflammatory meloxicam for the management of postoperative pain. By delivering sustained levels of both a potent anesthetic and a local anti-inflammatory agent directly to the site of tissue injury, HTX-011 was designed to deliver superior pain relief while reducing the need for systemically administered pain medications such as opioids, which carry the risk of harmful side effects, abuse and addiction. HTX-011 has been shown to reduce pain significantly better than placebo or bupivacaine alone in five diverse surgical models: hernia repair, abdominoplasty, bunionectomy, total knee arthroplasty and breast augmentation. HTX-011 was granted Fast Track designation from FDA in the fourth quarter of 2017 and Breakthrough Therapy designation in the second quarter of 2018. In the second half of 2018, Heron expects to submit a New Drug Application (NDA) to the FDA for HTX-011.

About CINVANTI (aprepitant) injectable emulsion

CINVANTI, in combination with other antiemetic agents, is indicated in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (HEC) including high-dose cisplatin and nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy (MEC). CINVANTI is an intravenous formulation of aprepitant, a substance P/neurokinin-1 (NK1) receptor antagonist. CINVANTI is the first intravenous (IV) formulation to directly deliver aprepitant, the active ingredient in EMEND capsules. Aprepitant (including its prodrug, fosaprepitant) is the only single-agent NK1 receptor antagonist to significantly reduce nausea and vomiting in both the acute phase (0 – 24 hours after chemotherapy) and the delayed phase (24 – 120 hours after chemotherapy). CINVANTI is the only IV formulation of an NK1 receptor antagonist indicated for the prevention of acute and delayed nausea and vomiting associated with HEC and nausea and vomiting associated with MEC that is free of polysorbate 80 or any other synthetic surfactant. Pharmaceutical formulations containing polysorbate 80 have been linked to hypersensitivity reactions, including anaphylaxis and irritation of blood vessels resulting in infusion-site pain. FDA-approved dosing administration included in the United States prescribing information for CINVANTI is a 30-minute infusion.

Please see full prescribing information at www.CINVANTI.com.

About SUSTOL (granisetron) extended-release injection

SUSTOL is indicated in combination with other antiemetics in adults for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide (AC) combination chemotherapy regimens. SUSTOL is an extended-release, injectable 5-HT3 receptor antagonist that utilizes Heron’s Biochronomer drug delivery technology to maintain therapeutic levels of granisetron for ≥5 days. The SUSTOL global Phase 3 development program was comprised of two, large, guideline-based clinical studies that evaluated SUSTOL’s efficacy and safety in more than 2,000 patients with cancer. SUSTOL’s efficacy in preventing nausea and vomiting was evaluated in both the acute phase (0 – 24 hours after chemotherapy) and delayed phase (24 – 120 hours after chemotherapy).

Please see full prescribing information at www.SUSTOL.com.

On August 7, 2018 ADC Therapeutics, an oncology drug discovery and development company that specializes in the development of proprietary antibody drug conjugates (ADCs), reported that the first patient has been dosed in its Phase II clinical trial intended to support the submission of Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) (Press release, ADC Therapeutics, AUG 7, 2018, View Source [SID1234596075]). The clinical trial is evaluating the efficacy and safety of ADCT-402 (loncastuximab tesirine) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

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At the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the Company presented interim Phase I data on ADCT-402 in 138 evaluable, heavily pre-treated lymphoma patients who had failed, or were intolerant to, any established therapy known to provide clinical benefit, with a median of three prior therapies. At the time, for the 49 response-evaluable patients in Part 1 of the study (dose escalation) with DLBCL who received ADCT-402 at doses greater than or equal to 120 μg/kg, the overall response rate (ORR) was 55 percent (27/49), with 18 patients achieving a complete response (37 percent) and 9 patients achieving a partial response (18 percent).

The primary endpoint of the Phase II, multi-center, open-label, single-arm trial is the ORR in patients treated with ADCT-402, as confirmed by central review. Secondary endpoints include assessments of duration of response, complete response rate, relapse-free survival, progression-free survival and overall survival, as well as safety, pharmacokinetics and health-related quality of life. The trial will enroll approximately 140 patients with relapsed or refractory DLBCL at multiple centers in the USA and Europe.

"We are pleased to have dosed the first patient in our registrational Phase II clinical trial evaluating ADCT-402 in patients with DLBCL who have relapsed and have refractory disease after two or more multi-agent treatment regimens. Our Phase I clinical trial of ADCT-402 in non-Hodgkin lymphoma showed significant activity in patients with DLBCL and an acceptable safety profile," said Jay Feingold, MD, PhD, Chief Medical Officer and Senior Vice President of Clinical Development at ADC Therapeutics. "Unfortunately, there is no effective treatment for patients with multiple relapsed and refractory DLBCL, so we are excited about the potential to improve outcomes in these patients with ADCT-402 in a single-arm trial. We anticipate reporting results from the Phase II trial in the third quarter of 2019 and are hopeful that the data will support our submission of a BLA to the FDA."

Alex Spira, MD, PhD, FACP, Director of Virginia Cancer Specialists Research Institute and Clinical Assistant Professor of Oncology at Johns Hopkins School of Medicine, added, "Patients with DLBCL who have relapsed or are refractory after second-line chemotherapy face a very poor prognosis. There is a

significant unmet need for an effective new treatment option for this patient population, and we believe ADCT-402 has the potential to help impact patient outcomes in this disease."

For more information about the Phase II clinical trial, please visit www.clinicaltrials.gov (identifier NCT03589469).

ADC Therapeutics also plans to initiate multiple combination studies with ADCT-402 in the fourth quarter of 2018.

About Diffuse Large B-Cell Lymphoma (DLBCL)

Non-Hodgkin lymphoma (NHL) is the seventh most common type of cancer in the U.S., and accounted for an estimated 4.3 percent of new cancer cases in 2017.1 Diffuse large B-cell lymphoma (DLBCL) accounts for nearly one-third (32.5 percent) of NHL.2 The most common initial treatment for patients with DLBCL is chemo-immunotherapy. Response to initial treatment is high, but more than half of patients do not have long-term disease control.3 The current standard of care for relapsed DLBCL is additional chemotherapy, which can be followed by stem cell transplantation (SCT). The prognosis for relapsed patients is poor, especially for those with chemotherapy-refractory disease with a short interval between remission and relapse or those who relapse after high-dose therapy and SCT. There is a significant unmet need for an effective treatment for patients with relapsed or refractory DLBCL.

About ADCT-402

ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized monoclonal antibody that binds to human CD19, conjugated through a linker to a pyrrolobenzodiazepine (PBD) dimer toxin. Once bound to a CD19-expressing cell, ADCT-402 is internalized into the cell where enzymes release the PBD-based warhead. CD19 is a clinically validated target for the treatment of B-cell malignancies. The PBD-based warhead has the ability to form highly cytotoxic DNA interstrand cross-links, blocking cell division and resulting in cell death. Preliminary data from a Phase I clinical trial in relapsed or refractory B-cell non-Hodgkin lymphoma demonstrate ADCT-402 has significant activity in patients with diffuse large B-cell lymphoma (DLBCL). ADCT-402 is also being evaluated in an ongoing Phase I clinical trial in patients with relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL). The U.S. Food and Drug Administration has granted orphan drug designation to ADCT-402 for the treatment of DLBCL and mantle cell lymphoma.