On November 9, 2018 BioSpecifics Technologies Corp. (NASDAQ: BSTC), a biopharmaceutical company that originated and continues to develop collagenase-based therapies with a first in class collagenase-based product marketed as XIAFLEX in the U.S. and Xiapex in Europe, reported its financial results for the third quarter ended September 30, 2018 and provided a corporate update (Press release, BioSpecifics Technologies, NOV 9, 2018, View Source [SID1234531193]).

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"We are encouraged by the positive data recently reported for CCH in two new potential indications. We announced positive topline results from our Phase 1 clinical trial of CCH for the treatment of uterine fibroids in October and our partner Endo announced positive data from the Phase 3 clinical trials of CCH for the treatment of cellulite in November. The preliminary safety and efficacy data from our uterine fibroids trial demonstrates the promising potential for CCH injection for the treatment of this highly prevalent women’s health disease for which very limited non-surgical options are available," said Thomas L. Wegman, President of BioSpecifics. "With regard to our commercial pipeline and revenues, we were pleased to see continued growth for our two marketed indications for XIAFLEX, Peyronie’s Disease and Dupuytren’s Contracture with 22 percent year-over-year revenue growth for the quarter."

Third Quarter 2018 Financial Results
BioSpecifics reported net income of $5.0 million for the third quarter ended September 30, 2018, or $0.69 per basic share and $0.69 per share on a fully diluted basis, compared to net income of $2.7 million, or $0.38 per basic share and $0.37 per share on a fully diluted basis, for the same period in 2017.

Total revenue for the third quarter ended September 30, 2018 was $8.2 million, compared to $6.5 million for the same period in 2017. The increase in total revenues for the quarterly period was primarily due to royalties associated with higher net sales of XIAFLEX in Dupuytren’s contracture and Peyronie’s disease partially offset by lower mark-up on cost of goods sold revenue in prepaid foreign mark-up on cost of goods sold revenue recognized under new revenue standard ASC 606, as of January 1, 2018.

Licensing revenue consists of licensing fees, sublicensing fees and milestones. BioSpecifics recognized licensing revenue for the third quarter ended September 30, 2018 of zero and $4,408 for the same period in 2017.

Research and development (R&D) expenses for the third quarter ended September 30, 2018 were $0.2 million compared to $0.4 million for the same period in 2017. The decrease in the 2018 period, as compared to the 2017 period, was mainly due to lower consulting fees associated with clinical costs and other R&D programs.

General and administrative expenses for the third quarter ended September 30, 2018 and 2017 were $2.2 million in each period.

Provision for income taxes for the third quarter ended September 30, 2018 were $1.1 million, compared to $1.5 million for the same period in 2017.

As of September 30, 2018, BioSpecifics had cash and cash equivalents and investments of $77.0 million, compared to $65.1 million as of December 31, 2017.

As of September 30, 2018, BioSpecifics had 7,283,528 shares of common stock outstanding.

XIAFLEX/CCH Pipeline Updates and Anticipated Upcoming Milestones

BioSpecifics manages the development of collagenase clostridium histolyticum (CCH) for the treatment of uterine fibroids and has the right to initiate the development of any new potential indication not licensed by Endo. Endo’s licensed indications include Dupuytren’s Contracture and Peyronie’s Disease, both approved and marketed; in addition to cellulite, adhesive capsulitis, human and canine lipoma, lateral hip fat and plantar fibromatosis. BioSpecifics has entered into different in-licensing and royalty agreements in respect of indications currently marketed and under development. It is company policy not to announce publicly royalty rates for potential future indications under development before commercialization. It is important to emphasize that in-licensing royalty rates vary from indication to indication and it should not be assumed that the in-licensing royalty rates for potential future indications will be the same as those for currently marketed indications.

Positive Topline Phase 1 Uterine Fibroid Data Reported in October: BioSpecifics announced positive topline results from the Phase 1 clinical trial of CCH for the treatment of uterine fibroids. The study met the primary endpoint of safety and tolerability with no observed clinically significant adverse reactions. Pharmacodynamic changes were noted in all secondary endpoints with the exception of apoptosis. Statistically significant reductions in collagen content were observed as compared to control fibroids with a median reduction of 39 percent (p<0.05), as well as statistically significant reductions in collagen distribution as compared to control fibroids with an average reduction in density of collagen bundles of 21 percent.
Positive Phase 3 RELEASE-1 and RELEASE-2 Cellulite Data Reported in November: Endo announced positive results from two Phase 3 studies, RELEASE-1 and RELEASE-2, of CCH for the treatment of cellulite with highly statistically significant levels of improvement in the appearance in the target buttock at Day 71 reported. The study achieved the primary endpoint (RELEASE-1, p=0.006 & RELEASE-2, p=0.002) of composite responder analysis demonstrating at least a 2-level composite improvement independently reported by patient and clinician on the photonumeric scales of cellulite severity. Secondary endpoints included both investigator and patient assessments of cellulite appearance as measured by CR-PCSS (Clinician Reported- Photonumeric Cellulite Severity Scale) and PR-PCSS (Patient Reported- Photonumeric Cellulite Severity Scale) scores, SRSS (Subject Self Rating Scale) and the Subject-Global Aesthetic Improvement Scale. Eight out of eight key secondary endpoints were achieved for RELEASE-1 and seven out of eight secondary endpoints were achieved for RELEASE-2. CCH was well-tolerated in actively treated subjects with most adverse events being mild to moderate in severity and primarily limited to the local injection area.
XIAFLEX Expected to Continue to Grow in the Low 20 Percent Range: XIAFLEX future growth initiatives continue to support the increase in disease state awareness for both Peyronie’s Disease and Dupuytren’s Contracture through direct to consumer campaigns.

On November 9, 2018 Aurinia Pharmaceuticals Inc., (NASDAQ:AUPH)(TSX:AUP) reported its Chairman and CEO, Richard Glickman, will participate in two upcoming investor conferences (Press release, Aurinia Pharmaceuticals, NOV 9, 2018, View Source [SID1234531092]).

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Wednesday, November 14, 2018, Aurinia will present a company overview at the Jefferies 2018 London Healthcare Conference in London, UK at 10:00am GMT. The presentation will be webcast live and can be accessed via the investor section of the Aurinia website, www.auriniapharma.com. A replay of will also be archived on the site following the event.

Tuesday, November 27, 2018, Aurinia will participate in One-on-One Meetings at the Evercore ISI HealthCONx Conference in Boston, MA.

On November 9, 2018 Harpoon Therapeutics, Inc. ("Harpoon"), a clinical-stage immunotherapy company developing a novel class of T cell engagers that harness the power of the body’s immune system to treat patients suffering from cancer and other diseases, reported preclinical data supporting the development of a new Protease-activated Tri-specific T cell Activating Construct ("ProTriTAC") platform (Press release, Harpoon Therapeutics, NOV 9, 2018, View Source [SID1234531108]). The new ProTriTAC platform is based on Harpoon’s Tri-specific T cell Activating Construct ("TriTAC") technology, which is designed to bind a patient’s immune cells to cancer cells. This binding leads to activation of the immune cell, which then attacks and kills the cancer cell. Data were presented at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Washington, D.C., held November 9-11, 2018.

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Therapeutics derived from the new ProTriTAC platform are intended to be administered as T cell inactive prodrugs and are optimized for serum exposure to ensure delivery to solid tumor tissues. At the site of the tumor, these prodrugs can be locally activated by tumor-associated proteases. This induces T cells to kill tumor cells expressing target antigen without affecting other tissues.

"We are very pleased to launch our ProTriTAC platform, which retains the advantages of our TriTAC platform, including activity at low levels of target expression, extended serum half-life and conventional manufacturing. Our ProTriTAC platform allows us to access tumor-associated antigens that have been historically challenging because they are expressed in both tumors and non-tumor tissues. ProTriTAC therapeutics are designed to be serum half-life extended, but do not engage T cells until they are clipped by tumor-associated proteases. Once clipped, a T cell activator is released at the site of the tumor. However, this T cell activator now has a short half-life and is quickly removed from circulation before it can impact non-tumor tissues," said Holger Wesche, PhD, Chief Scientific Officer of Harpoon. "Harpoon plans to bring its first ProTriTAC product candidate into IND-enabling studies in 2019."

"ProTriTAC is an important extension of Harpoon’s proprietary TriTAC platform, a T cell engager platform designed to harness the natural power of the patient’s own immune system to fight cancer and other diseases," said Jerry McMahon, PhD, President and CEO of Harpoon. "ProTriTAC product candidates have the potential to increase the number of possible tumor antigen targets for Harpoon’s emerging pipeline."

The poster entitled "ProTriTAC: A Protease-Activatable T Cell Engager Platform That Links Half-Life Extension to Functional Masking" can be found on the Publications page of Harpoon’s website. Key proof-of-concept data include:

Biological Activity Dependent on Protease Activation

Intact ProTriTAC proteins can block binding to T cells by more than 500-fold, but they can become fully active after a single proteolytic cleavage event, enabling T cell binding and activity in the tumor microenvironment.

Potent Anti-Tumor Activity In Vivo Is Protease-Dependent

When administered to tumor-bearing mice, ProTriTAC molecules can completely inhibit tumor growth with doses as low as 0.03 mg/kg. These data imply that this activity depends on proteolytic activation of the ProTriTAC in the tumor.

Reduced T Cell Binding and Rapid Clearance of the Active Drug in Non-Human Primates

Pharmacokinetic data derived from non-human primates confirm that ProTriTACs exhibit long serum half-life and support that T cells are not being engaged by the prodrug form.

On November 9, 2018 Aduro Biotech, Inc. (NASDAQ: ADRO) reported presentation of preliminary data from its ongoing Phase 1 dose-finding study of ADU-S100 (MIW815), a novel STING (stimulator of interferon genes) pathway activator, at SITC (Free SITC Whitepaper) 2018 in Washington, D.C. Aduro and collaborator Novartis embarked on this first-in-human trial (see www.clinicaltrials.gov, identifier NCT02675439) as an important first step in characterizing the safety profile and mechanism of ADU-S100 and its ability to activate the STING pathway (Press release, Aduro Biotech, NOV 9, 2018, View Source [SID1234531178]).

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Data Highlights from ADU-S100 Monotherapy Trial (Data cut-off: August 16, 2018)

The Phase 1 dose escalation and dose expansion clinical trial is designed to evaluate the safety, tolerability and clinical activity of ADU-S100 in patients with advanced, metastatic treatment-refractory solid tumors or lymphomas. In this multicenter, open-label trial, ADU-S100 is administered intratumorally on Days 1, 8 and 15 of a 28-day cycle.

The trial has enrolled 41 patients, with 40 patients evaluated for response. The median number of prior anti-cancer treatments was four (range 0-15). More than half of patients (53.7%) received prior therapy with a checkpoint inhibitor.

More than 20 types of cancer have been treated in this trial, including Merkel cell, parotid gland, colorectal, endometrial, ER+ and triple-negative breast cancer, esophageal, collecting duct carcinoma, ovarian, Hodgkin’s disease, hemangioepithelioma and other cancers.

Doses of 50-3200 mcg have been explored in this presentation; enrollment is ongoing for additional patient cohorts.

No dose-limiting toxicities have been reported at these dose levels. The most common (³10% of patients) treatment-related adverse events (TRAEs) were pyrexia, injection site pain and headache. Grade 3/4 TRAEs included increased lipase and elevated amylase, tumor pain, dyspnea, respiratory failure and injection site reaction.

Clinical and Biomarker Activity

Importantly, increases in key systemic cytokines, including IL-6, MCP-1 and IFN-ß, were observed after administration, indicating target engagement of ADU-S100 and activation of the STING pathway.

Two of the 40 patients treated had a partial response (PR) – one patient with Merkel cell carcinoma and one patient with parotid gland cancer who had received prior anti-PD-1 therapy.

11 patients achieved stable disease (SD), including five patients who had received prior checkpoint inhibitor therapy.

Three patients with SD remain on study and continue to receive treatment, including one patient with collecting duct carcinoma who has been on study for greater than one year.

On-treatment tumor biopsies showed increases in CD8+ T cells in injected tumors in a subset of patients, including those with Merkel cell, collecting duct and esophageal carcinomas. Aduro and Novartis are continuing to evaluate additional pathology and other biomarkers to assess the pharmacological activity of ADU-S100 in these patients.

"We are encouraged by the data obtained from the dose escalation portion of this first-in-human trial of ADU-S100 in heavily pre-treated patients with a diverse set of advanced cancers," commented Stephen T. Isaacs, chairman and chief executive officer of Aduro Biotech. "Based on the safety profile and interesting signals observed from the clinical approach to date, we expect to collect additional biomarker data and have begun to enrich monotherapy dose cohorts with additional patients of select tumor types. At the same time, we have expanded the breadth of our joint development program with our colleagues at Novartis to focus on combination with checkpoint inhibitors in melanoma and other homogeneous patient populations where we seek to deliver clinical benefit to patients in need."

In September 2018, this trial was amended to include a study arm evaluating ADU-S100 in combination with ipilimumab at its approved dose and schedule. Following a short dose escalation, the expansion phase aims to enroll patients with cutaneously and viscerally accessible melanoma who have relapsed or are refractory to PD-1 inhibitors.

Ongoing Phase 1b Trial of ADU-S100 + Anti-PD-1 Monoclonal Antibody Spartalizumab (PDR001)

A Phase 1b dose escalation and dose expansion clinical trial is ongoing to evaluate the safety and preliminary efficacy of ADU-S100 in combination with spartalizumab (PDR001), Novartis’ investigational anti-PD-1 monoclonal antibody (see www.clinicaltrials.gov, identifier NCT03172936). The multicenter, open-label trial is currently enrolling patients with advanced, metastatic treatment-refractory solid tumors or lymphomas and is evaluating two treatment schedules of ADU-S100 in dose escalation with a

fixed dose of spartalizumab. Patients in Group A receive a fixed dose of intravenous spartalizumab on day 1 and an intratumoral injection of ADU-S100 three times (day 1, 8, 15) in a 28-day cycle. Patients in Group B receive a fixed dose of intravenous spartalizumab on day 1 and an intratumoral injection of ADU-S100 on day 1 of every 28-day cycle.

The dose escalation combination trial has enrolled 50 patients with multiple cancers and who received multiple lines of prior therapies including prior immunotherapy.

Patients have been treated with full-dose PDR001 and increasing dosing of intratumoral ADU-S100 (50-400mcg); enrollment is ongoing for additional patient cohorts.

No dose-limiting toxicities have been reported.

In the early dosing cohorts of the ongoing study of ADU-S100 in combination with spartalizumab, preliminary observations include: 1) clinical responses observed in several tumor types, including two patients who had previously demonstrated responses to checkpoint inhibitor therapy alone; 2) reduced tumor volume in injected and non-injected lesions in some patients; 3) several patients remained on study longer than 6 months; and 4) safety profile consistent with what has been observed in the ADU-S100 monotherapy study.

Isaacs continued, "While still early, the preliminary observations emerging from initial dose cohorts of ADU-S100 plus spartalizumab are promising. In particular, the observation of clinical benefit in patients who received prior PD-1 therapy may provide further evidence supporting the synergy between STING and checkpoint inhibitor therapy that was previously demonstrated by our preclinical results. Extensive biomarker analysis is ongoing to assess biological activity. We and Novartis are committed to further exploration of the potential of ADU-S100 as a combination agent with both spartalizumab and ipilimumab in dose escalation and expansion into homogeneous patient populations. We look forward to seeing how these data evolve over time and expect to report on the results of these studies at future medical meetings."

About STING Pathway Activator Technology

The Aduro-proprietary STING pathway activator product candidates, including ADU-S100 (MIW815), are synthetic small molecule immune modulators that are designed to target and activate human STING. STING is generally expressed at high levels in immune cells, including dendritic cells. Natural activation of STING is not always sufficient to prevent the growth and spread of cancer cells. In preclinical models, ADU-S100 directly activates STING to further amplify the natural anti-tumor response. Once activated, the STING receptor initiates a profound innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of a systemic tumor antigen-specific T cell adaptive immune response.

Aduro’s lead molecule, ADU-S100, is the first therapeutic in development specifically targeting STING. In collaboration with Novartis, it is being tested in a Phase 1 clinical trial as a single agent and in combination with ipilimumab, and in a Phase 1b combination trial with spartalizumab (PDR001), an investigational anti-PD-1 monoclonal antibody. These studies are enrolling patients with cutaneously accessible, advanced/metastatic solid tumors or lymphomas. The trials are evaluating the ability of ADU-S100 to activate the immune system and recruit specialized immune cells to attack the injected tumor, leading to a broad immune response that seeks out and kills distant metastases.

On November 9, 2018 TESARO, Inc. (NASDAQ: TSRO), an oncology-focused biopharmaceutical company, today presented initial data from the Phase 1 AMBER trial of TSR-022 (anti-TIM-3 antibody) in combination with TSR-042 (anti-PD-1 antibody) in patients who have progressed following anti-PD-1 therapy treatment, in an oral session during the 2018 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference in Washington, D.C (Press release, TESARO, NOV 9, 2018, View Source [SID1234531194]). Additionally, Phase 1 GARNET data of TSR-042 in patients with previously treated recurrent/advanced non-small cell lung cancer (NSCLC) and Phase 1 monotherapy dose-escalation data for TSR-033 (anti-LAG-3 antibody) in a broad range of solid tumors were also highlighted in poster presentations.

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"The initial AMBER data featured at this year’s SITC (Free SITC Whitepaper) conference are the first clinical data to be presented for an anti-TIM-3 antibody in combination with an anti-PD-1 antibody and demonstrated that the combination of TSR-022 and TSR-042 is active and generally well tolerated in NSCLC and melanoma patients who have progressed following anti-PD-1 treatment," stated Mary Lynne Hedley, Ph.D., President and COO of TESARO. "Additionally, updated results from the GARNET trial demonstrated robust clinical activity of TSR-042 in previously treated, anti-PD-1 naive patients with recurrent or advanced NSCLC, the vast majority of which had TPS <50%. We look forward to presenting additional data from these studies in 2019."

A Phase 1 study of TSR-022, an anti-TIM-3 monoclonal antibody, in combination with TSR-042, an anti-PD-1 antibody (AMBER) [Oral presentation; Abstract: 10877; Poster: O21]

AMBER is an ongoing, open-label, Phase 1 study of TSR-022, an anti-TIM-3 antibody, in monotherapy or in combination with TSR-042, an anti-PD-1 antibody. The TSR-022 and TSR-042 combination portion of the study consists of dose-escalation and expansion cohorts. Data presented at SITC (Free SITC Whitepaper) included safety and efficacy data from the combination dose-escalation and two expansion cohorts: NSCLC patients that had progressed following anti-PD-1 treatment and melanoma patients that had progressed following anti-PD-1 treatment. Patients were treated with 100 milligrams or 300 milligrams of TSR-022 in combination with a fixed dose of TSR-042 (500 milligrams) every 3 weeks. A dose response trend was observed in both the NSCLC and melanoma cohorts based on greater clinical activity observed in patients treated with a 300 milligram dose of TSR-022 as compared to a 100 milligram dose.

At the time of data cutoff, 39 patients with NSCLC who had progressed following anti-PD-1 treatment had received treatment with the TSR-022 and TSR-042 combination, including 14 patients at the 100 milligram dose and 25 patients at the 300 milligram dose of TSR-022. Among the 11 evaluable patients treated with the 100 milligram dose of TSR-022, 1 had a confirmed partial response by immune related RECIST (irRECIST) criteria and 3 had stable disease. Among the 20 evaluable patients treated with the 300 milligram dose of TSR-022, 3 had confirmed partial responses and 8 had stable disease. All objective responses were in PD-L1 positive (TPS ≥ 1%) patients, indicating potential for biomarker enrichment. Sixteen patients had known PD-L1 positive tumors. Among the 12 evaluable patients with PD-L1 positive tumors treated with either the 100 or 300 milligram dose of TSR-022, 4 patients had confirmed partial responses (3 responses ongoing) and 6 had stable disease.

Preliminary safety findings indicate that the combination of TSR-022 and TSR-042 was generally well-tolerated. Pharmacokinetic analysis showed that a 300 mg dose is not sufficient to maintain maximal pharmacodynamic effect and suggests that a 900 milligram dose of TSR-022 should maintain a maximal effect in the vast majority of patients for the duration of the Q3W dosing interval. Patients with NSCLC who have progressed following anti-PD-1 treatment are currently being enrolled in the NSCLC expansion cohort at the 900 milligram dose of TSR-022 in combination with TSR-042. Additional data from this cohort (900 milligram dose) and the melanoma cohort (100 and 300 milligram doses) are expected in 2019.

GARNET: Preliminary safety, efficacy, pharmacokinetic, and biomarker characterization from a Phase 1 clinical trial of TSR-042 (anti-PD-1 monoclonal antibody) in patients with previously treated recurrent/advanced NSCLC [Poster: P326; Abstract: 10853]

GARNET is an ongoing Phase 1 study evaluating TSR-042 as a monotherapy in patients with advanced solid tumors. The ongoing cohort expansion portion of GARNET is evaluating TSR-042 at a dose of 500 milligrams every 3 weeks for the first 4 cycles and 1,000 milligrams every 6 weeks thereafter in four cohorts: MSI (microsatellite instability)-high endometrial cancer, MSI-high non-endometrial cancer, MSS (microsatellite-stable) endometrial cancer and previously treated recurrent / advanced anti-PD-1 naïve NSCLC. Data presented at SITC (Free SITC Whitepaper) included safety and efficacy data from the cohort of patients with NSCLC, which is fully enrolled.

At the time of data cutoff, 67 patients with previously treated recurrent / advanced anti-PD-1 naive NSCLC had received treatment with TSR-042, and 47 patients had at least one post-baseline tumor assessment or had discontinued treatment prior to first baseline assessment. Among these 47 patients, 15 had partial responses (including 2 unconfirmed responses that have not yet progressed) by irRECIST criteria for an overall response rate (ORR) of 31.9%; 14 additional patients (29.8%) had stable disease. Responses were durable and nine of the 15 responses are ongoing (60%).

The majority of patients (32 of 34; 94%) with available PD-L1 status had TPS <50% and clinical activity of TSR-042 was observed across all PD-L1 TPS categories. Among the 32 patients with low PD-L1 expression, 13 patients had TPS 1-49%, of which 5 had partial responses (ORR of 38.5%; including one unconfirmed response), and 19 patients had TPS <1%, of which 3 had partial responses (ORR of 15.8%).

Preliminary safety findings indicate TSR-042 was generally well-tolerated, with a safety profile characteristic of approved anti-PD-1 inhibitors for NSCLC.

The GARNET study is intended to support a Biologics License Application (BLA) submission to the U.S. Food and Drug Administration (FDA) in 2019 for patients with recurrent endometrial cancer.

A Phase 1 dose escalation study of TSR-033, an anti-LAG-3 monoclonal antibody, in patients with advanced solid tumors (CITRINO) [Poster Number: P325; Abstract: 10332]

Data from the monotherapy dose-escalation portion of the CITRINO study were presented and included 30 patients treated with different doses of TSR-033. There were no Grade ≥3 treatment-related treatment emergent adverse events reported. Exposure and peripheral receptor occupancy increased in a dose proportional manner from 20 milligrams to 720 milligrams.These preliminary findings indicate that TSR-033 was generally well tolerated across multiple dose levels, with a safety profile consistent to those of other immune checkpoint inhibitors.

Enrollment is ongoing for patients treated with TSR-033 in combination with 500 milligrams of TSR-042.

Investor Briefing and Webcast
TESARO will host an investor and analyst briefing in New York City on Monday, November 12 at 8:15AM local time. A reception will begin at 8:00AM ET, preceding the presentation. During the briefing, TESARO management will provide an overview of the Company’s immuno-oncology pipeline, followed by a detailed review of recent data presentations. The presentation will be followed by Q&A. This event will be webcast live and archived for 30 days, and may be accessed from the TESARO Investor Events and Presentations webpage at www.tesarobio.com.

About the AMBER Study
AMBER is an ongoing Phase 1 study of TSR-022, an anti-TIM-3 antibody, alone and in combination with TSR-042, an anti-PD-1 antibody. The study consists of two parts: dose escalation and cohort expansion. The monotherapy and combination dose-escalation parts of the study are complete. In the combination dose-escalation, patients were treated with 100 milligrams, 300 milligrams, or 900 milligrams of TSR-022 in combination with a fixed dose of TSR-042 (500 milligrams) every 3 weeks. The three expansion cohorts include NSCLC patients with progression following anti-PD-1 treatment, melanoma patients with progression following anti-PD-1 treatment, and colorectal cancer patients.

About the GARNET Study
GARNET is an ongoing multicenter, open-label, Phase 1 study of TSR-042 as a monotherapy in patients with advanced solid tumors. GARNET included a weight-based dose escalation study (Part 1) and a fixed-dose safety study (Part 2A), both of which have been completed. Results of these studies were used to determine the recommended Phase 2 dose (RP2D; 500 mg Q3W for the first 4 cycles then 1000 mg Q6W). The ongoing cohort expansion portion of GARNET is evaluating TSR-042 in four cohorts: MSI (microsatellite instability)-high endometrial cancer, MSI-high non-endometrial cancer, MSS (microsatellite-stable) endometrial cancer and previously treated recurrent / advanced anti-PD-1 naïve NSCLC.

About the CITRINO Study
CITRINO is an ongoing multicenter, open-label Phase 1 study evaluating TSR-033, an anti-LAG-3 antibody, alone or in combination with an TSR-042 in patients with advanced solid tumors in a broad range of solid tumors.

About TSR-042, TSR-022, and TSR-033
TSR-042 is an investigational humanized anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2. TSR-042 is the only anti-PD-1 therapy being studied as monotherapy every 3 weeks for 4 doses then every 6 weeks thereafter. TSR-042 was developed as part of the collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3 (TSR-075).