HyperAcute Pancreas (algenpantucel-L) / Lumos Pharma - LARVOL DELTA

A phase 1 study of alpha-1,3-galactosyltransferase-expressing allogeneic renal cell carcinoma immunotherapy in patients with metastatic renal cell cancer. (ASCO-GU 2017) - P1; "...Background: HyperAcute Renal (HAR) immunotherapy consists of two allogeneic renal cancer cell lines that have been genetically modified to express the carbohydrate α(1,3)Gal, to which humans have an inherent pre-existing immunity... RCC is considered an immunogenic tumor based on its response rate to immune checkpoint blockade and IL-2, occasional spontaneous regression, and the high level of tumor T cell infiltration. HAR was well tolerated in this patient population. Therefore, RCC is an appropriate tumor type to target with combination immunotherapy including HAR."

Checkpoint inhibition • P1 data • Renal Cell Carcinoma

Neoadjuvant therapy in pancreatic cancer: a review and update on recent trials. (PubMed, Curr Opin Gastroenterol) - "NAT is associated with improved survival for patients with borderline resectable PDAC but broader efficacy for resectable PDAC and optimal treatment strategy have yet to be defined."

Journal • Review • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

Long Term Follow-Up Study for Subjects Previously Treated With Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy (clinicaltrials.gov) - P=N/A | N=29 | Terminated | Sponsor: NewLink Genetics Corporation | Active, not recruiting ➔ Terminated; The IND was withdrawn

Trial termination • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

A Phase 3 Randomized Clinical Trial of Chemotherapy With or Without Algenpantucel-L (HyperAcute-Pancreas) Immunotherapy in Subjects with Borderline Resectable or Locally Advanced Unresectable Pancreatic Cancer. (PubMed, Ann Surg) - P3 | "Algenpantucel-L immunotherapy did not improve survival in patients with borderline resectable or locally advanced unresectable PDAC receiving SOC neoadjuvant chemotherapy and chemoradiation."

Clinical • Journal • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A PHASE III STUDY OF CHEMOTHERAPY WITH OR WITHOUT ALGENPANTUCEL-L (HYPERACUTE®- PANCREAS) IMMUNOTHERAPY IN SUBJECTS WITH BORDERLINE RESECTABLE OR LOCALLY ADVANCED UNRESECTABLE PANCREATIC CANCER (APCM 2019) - P3; "Patients were randomized to standard of care (SOC) FOLFIRINOX or gemcitabine/nab-paclitaxel chemotherapy alone or in combination with algenpantucel-L immunotherapy (HAPa) (IND# 12311), which consists of allogeneic pancreatic cancer cells engineered to express the murine (1,3)GT gene. In one of the largest pancreas cancer immunotherapy trials yet reported, the addition of algenpantucel-L immunotherapy was not associated with a survival advantage in patients with borderline resectable or locally advanced unresectable pancreatic adenocarcinoma when compared to SOC chemotherapy alone."

Clinical • P3 data

Immune Therapy in Pancreatic Cancer: Now and the Future? (PubMed) - "Combination of whole cell vaccine GVAX and mesothelin-secreting vaccine CRS-207 demonstrated an overall survival benefit in metastatic refractory pancreatic cancer patients. In the paper, we review the recently published and ongoing clinical trials using immune based treatment for pancreatic cancer."

Journal • Biosimilar • Oncology • Pancreatic Cancer

Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer: A phase 2 study (DDW 2012) - Presentation time: Tuesday, 8:00AM - 9:30AM; P2, N=70; NLG0205; The primary endpoints of median and 12-month DFS were 14.3 months and 63%, respectively, for the entire cohort; OS at one year in the entire cohort was 86% and compares favorably to 69% in historical controls; Addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival

P2 data • Pancreatic Cancer

Addition of algenpantucel-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer (ASCO 2012) - Presentation Time: Monday June 4, 8:00 AM to 12:00 PM; P2, N=70; NLG0305; 44 pts (63%) developed strong (G1-G3) skin reactions at the injection sites including many long term survival pts with periodic skin flares at injection sites far beyond their last vaccination; In 13/45 (29%) tested pts, an increase of >30% in anti-mesothelin Ab titer was seen after immunization; Thirty-nine (56%) presented with eosinophilia (range: 5- 45%), including one pt with persistent eosinophilia and stable lung metastasis for over 2 years

P2 data • Pancreatic Cancer

Immunotherapy Study for Surgically Resected Pancreatic Cancer (clinicaltrials.gov) - P3; N=722; Active, not recruiting; Sponsor: NewLink Genetics Corporation; Trial primary completion date: Mar 2015 ->Jun 2016

Trial primary completion date • Biosimilar • Immunology • Oncology • Pancreatic Cancer

18 YEARS OF PEDIATRIC LUNG TRANSPLANTATION: A COMING OF AGE. (IPTA 2017) - "...Immunosuppressive regimen included basiliximab induction, tacrolimus, mycophenolate (azathioprine in early cases) and steroids...Main postoperative complications included 1 (1.7%) hyperacute rejection, 25 (43.9%) acute cellular rejection and 8 (14%) acute humoral rejection... The advances reached in the last years, the surgical techniques, postoperative care, and immunosuppressive treatment make pulmonary transplant in children a well established reality. Our challenge is to decrease the incidence of chronic rejection and increase long term survival."

Retrospective data • Biosimilar • Cardiovascular • Fibrosis • Graft versus Host Disease • Idiopathic Pulmonary Fibrosis • Immunology • Retinopathy of Prematurity • Systemic Sclerosis

Production of heterozygous alpha 1,3-galactosyltransferase (GGTA1) knock-out transgenic miniature pigs expressing human CD39. (PubMed) - Transgenic Res - "The first barrier to successful xenotransplantation is hyperacute rejection, a rapid, massive humoral immune response directed against the pig carbohydrate GGTA1 epitope. The peripheral blood mononuclear cells (PBMC) from the transgenic pigs were more resistant to lysis by pooled complement-preserved normal human serum than that from wild type (WT) pig. Accordingly, GGTA1 mutated piglets expressing hCD39 will provide a new organ source for xenotransplantation research."

Journal • Biosimilar • Immunology • Venous Thromboembolism

The pathobiology of pig-to-primate xenotransplantation: a historical review. (PubMed) - Xenotransplantation - "The expression in GTKO/hCRP pigs of a human coagulation-regulatory protein, for example, thrombomodulin, is increasingly being associated with prolonged pig graft survival in non-human primates. Initial clinical trials of islet and corneal xenotransplantation are already underway, and trials of pig kidney or heart transplantation are anticipated within the next few years."

Journal • Review • Antibody-mediated Rejection • Biosimilar • Hemophilia • Inflammation

Q1 2012 results (NewLink Genetics) - Anticipated clinical data for P2 dose finding study in pancreatic cancer at both the 53rd Annual Meeting of the American Gastroenterological Association in conjunction with Digestive Disease Week on May 22, 2012 and the ASCO annual meeting on June 4, 2012.

Anticipated data • Anticipated P3 trial results • Pancreatic Cancer

Low dose vaccine study for surgically resected pancreatic cancer (clinicaltrials.gov) - P2, N=82; Active, not recruiting → Terminated (Sponsor proceeded with a phase III study for same indication); Completion date: Sep ’10 → Sep ‘12

Completion date • Trial terminated • Pancreatic Cancer

Hyperacute Extracranial Internal Carotid Artery Stenting vs Angioplasty: Which is the Best for Recanalization? (ISC 2017) - "... From 97 patients who underwent hyperacute revascularization of the extracranial ICA, 63 fulfilled the inclusion criteria: mean age 65.6±13.6 years, median time from symptoms onset to treatment 249 [161-330] minutes... Hyperacute extracranial ICA stenting seems to have a lower risk of restenosis compared to angioplasty, without a significant increase of complications and stroke recurrences"

Clinical • Biosimilar • Cardiovascular • Reperfusion Injury • Venous Thromboembolism

Peripheral sensory stimulation is neuroprotective in a rat photothrombotic ischemic stroke model. (PubMed) - Conf Proc IEEE Eng Med Biol Soc - "...Here, we investigated the potential neuroprotective effect of PSS during the hyperacute phase of stroke in a rat photothrombotic ischemia (PTI) model...Overall, the study demonstrated that PSS administered immediately following ischemia induction in a rat PTI model can significantly promote neuroprotection via inhibition of peri-infarct expansion and enhanced cortical neural activity functions, suggesting effective recovery. Future work utilizing multimodal imaging to probe changes in neurovascular functions, will explore application of PSS as an adjuvant intervention for improving rtPA thrombolysis therapy."

Journal • Biosimilar • Gene Therapies • Reperfusion Injury • Venous Thromboembolism

Effect of Blood Pressure During the Acute Phase on 3-month and 2-year Clinical Outcomes Among Patients With Ischemic Stroke (AHA 2016) - "Three BPs were measured every 2 hours for the first 24 hours (hyperacute phase), every 4 hours during the second and third days, and every 8 hours thereafter for the remainder of the seven days (acute phase). Spline analyses showed U-shaped associations between mean SBP in the acute phase and risk of death and major disability at 3 months or 2 years in the intervention group, with an optimal SBP level of 130-140 mm Hg. Our study indicated that mean SBP, but not its variability, during the acute phase was associated with risk of death and major disability among patients with ischemic stroke."

Clinical • Biosimilar • Reperfusion Injury

A Novel Treatment Using an Intraventricular Stent Graft for Postinfarction Ventricular Septal Rupture in a Porcine Model. (PubMed) - Innovations (Phila) - "The use of our new IVSG in this VSR animal experiment model significantly decreased the left-to-right shunt. The new device was able to control the acute heart failure associated with VSR with a minimally invasive procedure during the hyperacute phase of heart failure. Potential improvements in VSR treatment outcomes are expected with its clinical application."

Journal • Acute Coronary Syndrome • Biosimilar • Cardiovascular • Heart Failure

SAFETY OF HEAD DOWN TILT 15° IN EXPERIMENTAL INTRACEREBRAL HAEMORRHAGE: RELEVANCE FOR HYPERACUTE GRAVITATIONAL THERAPY IN ACUTE STROKE. (ESTOC 2017) - "Our findings indicate that HDT15° does not worsen hematoma expansion if applied in the hyperacute phase of experimental intracerebral haemorrhage. Further research is needed to effectively develop a HDT-based gravitational therapy for enhancing cerebral collateral flow in suspected hyperacute ischemic stroke."

Biosimilar • Cardiovascular • Reperfusion Injury • Venous Thromboembolism

NewLink Genetics Corporation reports first quarter 2012 financial results (Globe Newswire) - Enrollment for P3 trial in pancreatic cancer is expected to complete by Q4 2013; HyperAcute Pancreas P2 clinical trial data will be presented at both the 53rd Annual Meeting of the American Gastroenterological Association in conjunction with DDW on May 22, 2012 and the 2012 ASCO Annual meeting on June 4, 2012

Anticipated P2 data presentation • Anticipated P3 enrollment completion • Pancreatic Cancer

HyperAcute Pancreas - Biotech's 5 key attacks on pancreatic cancer (FierceBiotech) - P2, N=70; NLG0205; The trial met the primary objective with an established median DFS of 14.2 months and secondary endpoint of OS with 86% of those who'd received the vaccine alive after one year; The company expects to fully enroll its P3 trial (NLG0405) by 2013

Anticipated enrollment completion • P2 data • Pancreatic Cancer

Addition of algenpantucel-L immunotherapy to standard of care (SOC) adjuvant therapy for pancreatic cancer (ASCO 2012) - Presentation time: Mon, Jun 4; 8:00 AM - 12:00 PM; Anticipated presentation at ASCO 2012

Anticipated P3 data presentation • Pancreatic Cancer

NewLink genetics reports two- and three-year overall survival data from its phase-2 HyperAcute(R) Pancreas (algenpantucel-L) immunotherapy trial at the American Society of Clinical Oncology (ASCO) Annual meeting (ASCO 2012, Globenewswire) - P2. N=69; Study ID: NLG0205; The median DFS was 14.1 months; 12-month OS was 86%; The predicted 12 month OS in the study was 63%; Subgroup analysis showed that pts receiving 300 million cells/dose had a 12-month DFS of 81% and OS of 96%, while those receiving 100 million cells/dose had an 12-month DFS of 51% and OS of 79% (p=0.053, Fisher's Exact)

P2 data • Pancreatic Cancer

NewLink genetics reports two- and three-year overall survival data from its phase-2 HyperAcute(R) Pancreas (algenpantucel-L) immunotherapy trial at the American Society of Clinical Oncology (ASCO) Annual meeting (ASCO 2012, Globenewswire) - P2. N=69; Study ID: NLG0205; The median DFS was 14.1 months; 12-month OS was 86%; The predicted 12 month OS in the study was 63%; Subgroup analysis showed that pts receiving 300 million cells/dose had a 12-month DFS of 81% and OS of 96%, while those receiving 100 million cells/dose had an 12-month DFS of 51% and OS of 79% (p=0.053, Fisher's Exact)

P2 data • Pancreatic Cancer

Addition of algenpantucel-l immunotherapy to standard adjuvant therapy may improve overall survival (os) and disease-free survival (dfs) in resected pancreas cancer patients (APC2011) - P=NA, N=70; Current median DFS of 16 months compares favorably to the 11 months observed in RTOG-9704; OS data continues to mature, with 74% still censored; Algenpantucel-L was well tolerated with no likely/directly attributable grade 3 SAEs

Clinical data • Pancreatic Cancer