ANTICIPATED APPROVAL. Priority Review. Priority Review

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1 PIPELINE DRUG CURRENT STATUS ANTICIPATED APPROVAL WHAT IS THE DRUG BEING DEVELOPED FOR? adapalene gel 0.1% (Differin Rxto-OTC - Galderma) July 2016 Rx-to-OTC conversion of Differin (adapalene 0.1% gel) for persons aged 12 years or older with acne; topical therapy. andexanet alfa (AndexXa - Portola/Bayer) BLA Filed /17/2016 Priority Review Andexanet alfa is being developed for use as a Factor Xa inhibitor reversal agent. It works by binding to Factor Xa inhibitors such as Xarelto (rivaroxaban) that are used to prevent clotting, but may need to be reversed for emergency surgery or life-threatening bleeding events; intravenous therapy. Breakthrough Therapy benzhydrocodone / APAP (Apadaz -KemPharm) Complete Response 2017 Priority Review Prodrug of hydrocodone, combined with acetaminophen, for the treatment of pain. This drug may exhibit unique abuse deterrent properties and lower incidence of opioidinduced constipation; oral therapy. bezlotoxumab (MK-3415A - Merck) BLA Filed /23/2016 Priority Review Monoclonal antibody that neutralizes toxin B for preventing recurrence of Clostridium difficile infections and Clostridium difficile-associated diarrhea (CDAD); intravenous therapy. ertugliflozin (Merck / Pfizer) Phase A sodium glucose cotransporter 2 (SGLT2) inhibitor for treating type 2 diabetes. Blocking this receptor results in excretion of excess glucose in the urine, decreasing blood glucose levels; oral therapy. granisetron, s.r. inj (Sustol - Heron) 2Q:2016 Sustol is a long-acting formulation of the 5-HT3 antagonist granisetron (Kytril Roche/generics) for the prevention of chemotherapy-induced nausea and vomiting. This product is dosed every three to five days; subcutaneous injection.

2 PIPELINE DRUG CURRENT STATUS ANTICIPATED APPROVAL WHAT IS THE DRUG BEING DEVELOPED FOR? house dust mite SL immunotherapy (HDM SLIT - Merck) BLA Filed /10/2017 MK8237 is a sublingual tablet for use as immunotherapy for the treatment of house dust mite (HDM) allergy; sublingual therapy. hydrocodone e.r. (Vantrela Teva) A twice-daily extended-release formulation of hydrocodone bitartrate, formulated with an abuse-deterrent technology called Onguard, which used multi-layered, gel-forming polymer coating of the opioid particles; oral therapy. insulin aspart (NovoRapid Novo Nordisk) 12/09/2016 Ultra-fast acting insulin for treating type 1 and type 2 diabetes mellitus; subcutaneous therapy. insulin degludec / liraglutide (Xultophy - Novo Nordisk) 07/25/2016 A combination of Novo Nordisk's insulin degludec (Tresiba) and its GLP-1 analogue Victoza (liraglutide) for treating type 2 diabetes; subcutaneous therapy (once daily). insulin glargine (Basaglar - Lilly / BI) Approved /15/2016 Basaglar has the same amino acid sequence as Lantus (insulin glargine - Sanofi). This product will be a Lantus competitor; subcutaneous therapy. lifitegrast (Shire) 7/22/2016 Priority Review A non-steroidal, small molecule, integrin inhibitor that blocks chronic inflammation mediated by T-cells that can result in dry eyes. This product is under review for treating dry eyes in adults; ophthalmic therapy (twice daily). lixisenatide (Lyxumia - Sanofi) July 2016 Glucagon-like peptide-1 receptor agonist for treating type 2 diabetes; subcutaneous injection (once daily).

3 PIPELINE DRUG CURRENT STATUS ANTICIPATED APPROVAL WHAT IS THE DRUG BEING DEVELOPED FOR? lixisenatide/insulin glargine (iglarlixi Sanofi) August 2016 Sanofi is combining its investigational GLP-1 analog with the company s Lantus for the treatment of patients with Type 2 diabetes uncontrolled on anti-diabetic treatment; subcutaneous therapy. morphine sulfate e.r. (Arymo ER - Egalet) 10/14/2016 Abuse-deterrent formulation of morphine sulfate ER. This product will be available in similar dosage strengths as MS Contin (morphine sulfate); oral therapy. oxycodone / naltrexone e.r. (Troxyca ER Pfizer) An extended-release formulation of a fixed-dose combination of oxycodone (20mg) and naltrexone (2.4mg) for the treatment of moderate-to-severe pain; oral therapy. oxycodone, extended-release (Remoxy Pfizer) Phase /25/2016 Priority Review Abuse-resistant long-acting (twice daily) oral formulation of oxycodone for round-the-clock treatment of persistent pain. When crushed, the Remoxy gel-cap yields a viscous gel presumably too thick to snort or inject; oral therapy. oxymetazoline 1% topical cream (AG Allergan) NDA Filed Q:2017 Oxymetazoline 1% cream formulation of the alpha 1 and 2 adrenergic agonist for treatment of persistent erythema associated with rosacea; topical therapy. solithromycin (CEM101 Cempra) December 2016 Fourth generation fluoroketolide (macrolide) antibiotic (Protein 5OS ribosomal subunit inhibitor) for treating community acquired bacterial pneumonia (CABP). It is expected to be the first macrolide antibiotic available as an intravenous, oral, and pediatric suspension formulations in over 20 years. Product expected to receive approval in 2016, but launched in 2017.

4 PIPELINE DRUG CURRENT STATUS ANTICIPATED APPROVAL WHAT IS THE DRUG BEING DEVELOPED FOR? testosterone undecanoate (LPCN 1021 lipocine) 06/28/2016 LPCN 1021 is a twice-daily oral testosterone replacement therapy for treating hypogonadal men with low testosterone; oral therapy.

5 Brand Drug Detail Current Status: Route of Administration/Dosing: adapalene gel 0.1% (Differin Rx-to-OTC - Galderma) This product is currently under FDA review. FDA is expected to rule on the Rx-to-OTC conversion of Differin 0.1% during the second half of Differin Gel should be applied once a day to affected areas in the evening after washing. Rx-to-OTC conversion of topical adapalene gel (0.1%) for treatment of acne vulgaris in patients 12 years of age and older. Adapalene is a third-generation topical retinoid that inhibits comedone formation and inflammation. Biochemical and pharmacological profile studies have demonstrated that adapalene is a modulator of cellular differentiation, keratinization, and inflammatory processes all of which represent important features in the pathology of acne vulgaris. Acne is the most common skin condition in the United States. Without treatment, dark spots and permanent scars can appear on the skin as acne clears. Although commonly affecting teens, it can also impact people in their 30s, 40s, 50s, and beyond. Comments: The U.S. Food and Drug Administration (FDA) approved Differin (adapalene gel 0.1%) in 1996 as a prescription-only product. Currently, 0.1% gel (the Rx-to-OTC) candidate is the most widely prescribed formulation. It is also available as 0.1% cream, 0.3% gel and in formations combined with benzoyl peroxide. On April 15, 2015, FDA s Nonprescription Drugs Advisory Committee voted unanimously to recommend over-the-counter marketing of adapalene gel 0.1% for persons aged 12 years or older with acne. FDA will review the advisory committee s recommendations with possible approval in the second half of 2016.

6 andexanet alfa (AndexXa - Portola/Bayer) Current Status: This product is currently under FDA review with an action date of Aug. 17, Route of Administration/Dosing: Intravenous (IV) therapy Universal Factor Xa (FXa) inhibitor antidote, to reverse the activity of FXa inhibitors and low molecular weight heparin (LMWH) in patients experiencing a major bleeding event or require emergency surgery Andexanet alfa is a recombinant protein that is structurally distinct from native FXa, and acts as a decoy for FXa inhibitors in the blood; this prevents them from inhibiting the activity of native FXa, thereby allowing native FXa to participate in restoring hemostasis. One of the major drawbacks to the new oral anticoagulants (Factor Xa Inhibitors) is that a reversal agent is currently not available. To alleviate bleeding associated with these anticoagulants, providers have utilized prothrombin complex concentrates (activated, three-factor, four-factor), recombinant factor VIIa, and/or fresh frozen plasma. Annually, around 1-4% of patients treated with Factor Xa inhibitors may experience major bleeding and 1% may require emergency surgery. Est. Annual Sales (Millions): $355 Global Sales (2020) Estimated Cost of Therapy: Portola is currently undertaking a pricing study and suggests that it is considering a price north of Praxbind's $7,000 but lower than Vorazaze's $50K (MTX toxicity). No direct acting reversal agents available. Platelet transfusion required for rapid reversal. Praxbind (idarucizumab) approved on 10/16/2015 (Pradaxa only). Pipeline Product(s): aripazine (PER977 - Perosphere): Phase 2/3 (2017) Comments: Potential first-in-class recombinant, modified Factor Xa molecule that is being developed as an antidote for patients receiving a Factor Xa inhibitor who suffer a major bleeding episode or who may require emergency surgery. As there are no specific reversal agents for factor Xa inhibitors yet, andexanet alfa potentially addresses an unmet need. Andexanet alfa is being developed as a "companion" product to betrixaban, Portola's once-daily, oral Factor Xa inhibitor. Betrixaban could also be approved in The product is designed to induce clotting for either the treatment of acute bleeding, or to prevent such bleeding in those undergoing surgery who are currently on FXa inhibitors or LMWH for other medical conditions. Results from ANNEXA-R study (phase III) demonstrated that andexanet alfa rapidly and significantly reversed the anticoagulant effect of rivaroxaban as measured by anti-factor Xa activity (>90 percent reduction of mean anti-factor Xa activity within five minutes of the end of administration) compared with placebo (p<0.0001). Portola released positive top-line data from the second part of andexanet s Phase 3 ANNEXA-R trial. The study demonstrated that administration of an intravenous bolus of andexanet alfa followed by a continuous twohour infusion produced rapid reversal of the anticoagulant effect of rivaroxaban and sustained it for the duration of the infusion. The FDA has accepted the drug application, with expected review on 08/17/2016.

7 Current Status: Route of Administration/Dosing: benzhydrocodone / APAP (Apadaz - KemPharm) Complete Reponses Letter issued Oral therapy Treatment of acute moderate to moderately severe pain Immediate-release formulation of a prodrug of hydrocodone. Prodrug must be metabolized by the GI tract in order to exhibit the opioid effects. According to the CDC, health care providers wrote 259 million prescriptions for painkillers in Comments: Benzhydrocodone (contracted from benzoate-hydrocodone) is an immediate-release formulation and a prodrug of hydrocodone. It has unique physicochemical and pharmacological attributes that may deliver additional patient benefits, including reduced potential for abuse and reduction or elimination of opioid-induced constipation (Phase 3 trials ongoing). NDA filing planned in KP201 is a new molecular entity (NME) prodrug with a new chemical name, benzhydrocodone, and if approved, KemPharm expects it will have a lower prescribed milligram strength than the therapeutic equivalent amount of hydrocodone bitrate used in existing IR hydrocodone/apap combination products. These differences will mean there will be no generic equivalent product for KP201/APAP, making substitution difficult at the pharmacy. 03/10/ FDA granted the product a priority review. The PDUFA date is June 9, /19/ Kempharm presented an abuse-liabilty study at the 2016 AAPM Annual Meeting. In the trial(kp201.a01), it was observed that KP201/APAP was associated with lower exposure to hydrocodone at the 8 and 12 tablet doses compared to Norco (hydrocodone bitartrate/apap), while exposure at the low-dose (4 tablets) was bioequivalent. Approximately 25% and 34% of subjects demonstrated a 20% or greater reduction in Cmax and AUC0-1 measures of exposure to hydrocodone, respectively, within the first hour at the 12 tablet dose of KP201/APAP as compared to an equivalent dose of Norco. The safety profile of KP201/APAP was comparable to that of Norco. In addition, the 8 and 12 tablet doses of KP201/APAP showed a lower incidence of hypoxia as compared to equivalent doses of Norco. Drug liking, as measured by Emax on the Drug Liking Visual Analogue Scale (DL-VAS), was similar for KP201/APAP and Norco at each equivalent dose. KemPharm believes this may be due to the large amount of APAP acting as a second analgesic. These results demonstrate that KP201/APAP may potentially lower exposure to hydrocodone and reduce the incidence of hypoxia at high oral doses, suggesting the potential for improved safety following overconsumption or overdose of KP201/APAP, explained Sven Guenther, Ph.D., Executive Vice President of Research and Development for KemPharm. "Additional trials are planned to further explore the potential safety benefits of KP201. We are not aware of any other opioid that shows a reduction in relative exposure at high doses. On May 5, 2016, an FDA advisory committee voted 16-4 in favor of approval, but voted (18-2) against abuse-deterrent labeling. 06/14/2016 Update: Complete response issued, delaying final approval.

8 bezlotoxumab (MK-3415A - Merck) Current Status: This product was granted a priority review and is currently under FDA review with an action date of July 23, Route of Administration/Dosing: Intravenous (IV) therapy An antitoxin given in conjunction with standard of care antibiotics that are used in the treatment of C. difficile infections. Bezlotoxumab is a humanized monoclonal antibody designed to neutralize C. difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to C. difficile-associated diarrhea. According to the CDC, C. difficile was estimated to cause almost half a million infections in the United States in 2011, and 29,000 died within 30 days of the initial diagnosis. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections, making C. difficile a very important cause of infectious disease death in the United States. C. difficile causes an inflammation of the colon and deadly diarrhea. While initial antibiotic treatment for C. difficile is often successful, up to 35% of patients experience a recurrence of the infection, with each recurrence increasing the risk for future recurrences. Merck thinks the drug could prevent almost 50,000 infections with C. difficile a year. Comments: Bezlotoxumab is an investigational antitoxin given in conjunction with standard of care antibiotics that are used in the treatment of C. difficile infection. The product is not an antibiotic. Bezlotoxumab is designed to neutralize C. difficile toxin B, a toxin that can damage the gut wall and cause inflammation, leading to C. difficile-associated diarrhea. The FDA accepted Merck s Biologics License Application and granted priority review to Bezlotoxumab, an antitoxin for the prevention of C. difficile infection, in January Merck's MODIFY I and MODIFY II studies showed that bezlotoxumab as a monotherapy was associated with lower rates of recurrent infection compared to placebo (17.4% vs. 27.6% in MODIFY I and 15.7% vs. 25.7% in MODIFY II) for recurrence in patients on antibiotics. MODIFY I and II were global phase 3 trials that demonstrated the safety and efficacy of a single 10 mg/kg IV dose of bezlotoxumab (Merck) to decrease C. difficile recurrence when paired with standard antibiotic therapy. While initial antibiotic treatment for C. difficile is often successful, up to 35% of patients experience a recurrence of the infection, with each recurrence increasing the risk for future recurrences. On Jan. 27, 2016, Merck announced that FDA has accepted for review the Biologics License Application (BLA) for bezlotoxumab. The FDA granted Priority Review for bezlotoxumab with an action date of July 23, An FDA Advisory Committee met to discuss bezlotoxumab on 6/9/16 and the Advisory Committee voted 10-5 in its favor of approval. However, some panelists criticized Merck for the size of the Phase 3 program and other perceived shortcomings. Current Status: Route of Administration/Dosing: ertugliflozin (Merck / Pfizer) Phase 3 clinical trials Once daily oral therapy For use as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Ertugliflozin is an inhibitor of subtype 2 sodium-glucose transport protein (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney (SGLT1 being responsible for the remaining 10%). Approximately 25.8 million Americans have diabetes. Spending on diabetes medications totaled $22 billion in 2012, according to IMS Health. Type 2 Diabetes (T2D) is the most common type, accounting for an estimated 90 percent of all diabetes cases. Diabetes is a chronic disease that occurs when the body either does not properly produce, or use, the hormone insulin. Diabetes was estimated to cost the U.S. $245 billion in direct medical costs and reduced productivity in Est. Annual Sales (Millions): $470 Global Sales (2020) Invokana (canagliflozin - Janssen), Farxiga (dapagliflozin - AZ) and Jardiance (empagliflozin - Lilly) Pipeline Product(s): bexagliflozin (Chugai) - SGLT-2 inhibitor - Phase 3; sotagliflozin (Lexicon) - SGLT-1 and SGLT-2 inhibitor - phase 2 Comments: Merck and Pfizer announced that they are entering a partnership to develop ertugliflozin for type 2 diabetes. Ertugliflozin is a sodium-glucose linked transporter-2 (SGLT-2) inhibitor that comes in a once-daily pill. Originally, Pfizer was developing and testing ertugliflozin as a drug to be taken alone. However, this partnership will allow the companies to also develop ertugliflozin combination pills: ertugliflozin plus Merck s DPP-4 inhibitor Januvia (sitagliptin) and ertugliflozin plus Januvia and metformin. These combinations should make taking medication much easier, since they will reduce the number of pills from two or three to one. 03/04/ During its earning call, the company indicated plans to file ertugliflozin in 2016, as both single agent and in combination with Januvia.

9 granisetron, SR. inj (Sustol - Heron) Current Status: This product is currently under FDA review. Approval expected mid-2016 Route of Administration/Dosing: Subcutaneous (SQ) therapy dosed every 5 days. Treatment or prevention of acute- and delayed-onset chemotherapy-induced nausea and vomiting (CINV) after moderatelyor highly-emetogenic chemotherapy. Selective 5-hydroxytryptamine-3 (5-HT3) receptor antagonist Chemotherapy-induced nausea and vomiting is a large market opportunity. With approximately 7m annual chemo doses, about 75% generally result in nausea and vomiting and is a leading cause for patients to discontinue chemotherapy if left untreated. Sustol would provide another treatment option for these patients. Est. Annual Sales (Millions): $420 U.S. Sales (2023) Generically available 5-HT3 antagonist (Zofran, Kytril, Anzemet). This product will also compete with Aloxi (patent on injectable expires 9/30/2018; generics to oral formulations pending). Comments: SUSTOL (granisetron) Injection, extended release formulation of granisetron for the prevention of chemotherapy-induced nausea and vomiting (CINV). Sustol has been shown to maintain therapeutic drug levels of granisetron for at least five days with a single SQ injection. It is being developed for the prevention of both acute (day 1 following the administration of chemotherapy agents) and delayed (days 2-5 following the administration of chemotherapy agents) CINV associated with moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). While other 5-HT3 antagonists are approved for the prevention of CINV, SUSTOL is the first agent in the class to demonstrate a reduction in the incidence of delayed CINV in patients receiving HEC, a major unmet medical need, in a randomized Phase 3 study (MAGIC study). The FDA did not provide a specific timeline for completing its review of Sustol. house dust mite SL immunotherapy (HDM SLIT - Merck) Current Status: This product is currently under FDA review with an estimated action date of Feb. 10, 2017 Route of Administration/Dosing: Sublingual therapy (once daily) Sublingual immunotherapy dissolvable tablet designed to help treat allergic rhinitis with or without conjunctivitis caused by house dust mite-specific allergens. Immunotherapy (allergy shots) work by gradually increasing the person's tolerance to the allergy trigger. House dust mites are a source of a common perennial allergen and frequently live in household objects such as upholstered furniture, bedding and carpeting. It is estimated that about 20 million Americans have dust mite allergies. Comments: House dust mite-induced allergic rhinitis is a disease accompanied by nasal symptoms such as sneezing, runny nose, nasal congestion, and nasal itching due to an allergy to house dust mites. Allergen immunotherapy is a therapeutic method of administering the causative allergen of an allergic disease at a low dose at first and then an increased dose in order to reduce hypersensitivity to the allergen. Dust mite allergies are commonly treated it with over the counter medications, such as decongestants, antihistamines and nasal steroids. Immunotherapy (allergy shots) work by gradually increasing the person's tolerance to the allergy trigger. Merck's HDM SLIT will provide another treatment option for patients suffering dust mite allergies.

10 hydrocodone ER. (Vantrela - Teva) Current Status: This product is currently under FDA review with an action date in the fourth quarter of Route of Administration/Dosing: Twice-daily, acetaminophen-free hydrocodone designed with potential abuse-deterrent properties; oral therapy. hydrocodone bitartrate extended release tablets for the management of pain severe enough to require daily, around-theclock, long-term opioid treatment. CEP is a twice daily extended-release (ER), formulation of hydrocodone bitartrate formulated with an abuse-deterrent technology called Onguard, which uses multi-layered, gel-forming polymer coating of the opioid particles; oral therapy. Teva estimates that more than 100 million Americans are living with the distress of chronic pain Generically-available, immediate-release hydrocodone/apap combination; Zohydro ER (hydrocodone ER - Zogenex); Hysingla ER (hydrocodone ER - Purdue) Pipeline Product(s): Zohydro (hydrocodone e.r. - Zogenex) - crush-resistant (2017) Comments: CEP is an investigational twice-daily, acetaminophen-free hydrocodone formulation in development for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate. Study 3103 utilized a randomized, double-blind, placebo controlled randomized-withdrawal design to evaluate the efficacy and safety of an abuse-deterrent formulation of extendedrelease hydrocodone bitartrate at doses ranging from 30mg to 90mg every 12 hours. All patients (both placebo and active arms) were administered CEP in an open label phase to identify the maintenance dose that provided adequate analgesia with acceptable tolerability. Responders were then randomized to receive either placebo or their identified maintenance hydrocodone dose. The trial measured the changes in patients weekly average Worst Pain Intensity (WPI) between randomization and week 12 of treatment. After randomization, patients who continued receiving CEP maintained their improved WPI score whereas patients who were randomized to receive placebo had a significant worsening of their WPI compared to baseline (0.07 for CEP-3327 vs for placebo, p<0.001). Significant improvement in patients pain scores for the weekly API was also achieved (p<0.001) when an analysis was performed in patients randomized to continue receiving CEP in comparison to those randomized to receive placebo. On February 25, 2015, Teva announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) for the company s hydrocodone bitartrate extended-release (ER) tablets formulated with Teva s proprietary abuse deterrence technology (CEP-33237). An estimated PDUFA date would fall within the fourth quarter of 2015 (actual NDA filing date not disclosed). According to Teva, the PDUFA date is Oct. 23, /11/2015: The action date has passed with no updates. On June 7, 2016 the committees will discuss an NDA for CEP to treat pain severe enough to require a continuous, around-the-clock opioid analgesic when alternatives are inadequate. The twice-daily, acetaminophen-free hydrocodone bitartrate extended-release (ER) tablets are formulated with an abuse-deterrent technology. insulin aspart (NovoRapid - Novo Nordisk) Current Status: This product is currently under FDA review with an action date of Dec. 9, 2016 Route of Administration/Dosing: Subcutaneous therapy, likely administered similar to the company's NovoLog, which is generally administered immediately (within 5-10 minutes) prior to the start of a meal A rapid-acting insulin analog indicated to improve glycemic control in adults and children with diabetes mellitus. Insulin aspart is a rapid-acting insulin analog found in the company's NovoLog. However, it is combined with other excipients (nicotinamide and arginine) which results in a stable formulations with faster initial absorption after S.C. injection According to the CDC, about 30 million Americans have diabetes. Of them, approximately 6 million use insulin. Comments: A faster insulin would also be more convenient than current rapid-acting insulins, which are recommended to be taken about 30 minutes before meals. Newer ultra-rapid-acting insulins could also be associated with less hypoglycemia (and thus, potentially less weight gain) if the insulins can drop blood glucose more quickly, patients would be less likely to stack insulin and experience delayed hypoglycemia.

11 insulin degludec / liraglutide (Xultophy - Novo Nordisk) Current Status: This product is currently under FDA review with an action date of July 25, 2016 Route of Administration/Dosing: Once daily subcutaneous administration Treatment of patients with type 2 diabetes requiring therapy with both a long-acting basal insulin and a GLP-1 analog. Tresiba (insulin degudec) is a long-acting basal insulin, a hormone that prompts the update of glucose into the liver and muscle cells. Victoza (liraglutide) is a Glucagon-Like Peptide-1 (GLP-1) analog that helps lower blood glucose levels via several mechanisms, including increasing insulin secretion, decreasing glucagon secretion and delaying gastric emptying slowing glucose absorption. Patients will be able to administer both drugs in a single injection, eliminating the need for two injections per day in some individuals with Type 2 diabetes. Single agents, including long acting insulins and GLP-1 analogs. Pipeline Product(s): LixiLan (lixisenatide / insulin glargine - Sanofi) - Under FDA Review with an action date of 06/23/2016. Comments: Xultophy (proposed brand name) is a combination for the company's recently approved ultra -long acting insulin, Tresiba (insulin degludec), and the company's successful GLP-1 analog, Victoza (liraglutide). It will likely be used in patients with type 2 diabetes requiring therapy with both agents to control their blood glucose levels. The long-acting insulin primarily works by lowering fasting blood glucose levels. The GLP-1 analog helps to control postprandial (after mealtime) blood glucose levels. Therapy with Victoza has also resulted in weight loss, one of the risk factors associated with type 2 diabetes. According to press releases, the review date for this product is July 25, Sanofi's combination product (LixiLan [lixisenatide/insulin glargine]) could also receive approval by yearend /24/2016: FDA Advisory Committee voted 16-0 in favor of approval. insulin glargine (Basaglar Lilly / BI) Current Status: This product is currently "tentatively approved". Full approval is expected in December 2016, prior to launch. Route of Administration/Dosing: Once-daily subcutaneous (SQ) injection Injectable treatment for diabetes LY is a form of insulin glargine for use as an injection. Insulin glargine is a recombinant human insulin analog that is a long-acting blood-glucose lowering agent. Insulin and its analogs lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. LY is expected to have a flatter and more prolonged profile than the Lantus (100 units/ml) If approved LY would provide patients with another form of once daily insulin analog. An estimated 22.5 million adults will be diagnosed with type 2 diabetes by In the US, basal insulin market is estimated at more than $6 billion. Est. Annual Sales (Millions): $658 U.S. Sales (2020) Lantus (insulin glargine Sanofi), Toujeo (insulin glargine Sanofi), Levemir (insulin detemir -Novo Nordisk), Tresiba (insulin degludec - Novo Nordisk) Pipeline Product(s): Biosimilars to Lantus (Merck and Mylan) - could reach the market 2017/2018. Comments: LY is a new insulin glargine with the same amino acid sequence as Lantus, however it contains unspecified characteristic differences. This erosion could accelerate more quickly now that a second player (Merck) is also likely to enter in the 2016 timeframe. 10/14/2015 Update: Lilly/BI and Sanofi have reached a patent settlement agreement, allowing Basaglar to launch on Dec. 15, 2016.

12 lifitegrast (Shire) Current Status: This product is currently under FDA review with an action date of July 22, 2016 Route of Administration/Dosing: Twice-daily lifitegrast 5.0% ophthalmic solution Treatment of signs and symptoms of dry eye disease in adults Lifitegrast is a novel small-molecule integrin inhibitor. It binds to the integrin LFA-1 (lymphocyte function-associated antigen- 1), a cell surface protein found on leukocytes, and blocks the interaction of LFA-1 with its cognate ligand ICAM-1 (intercellular adhesion molecule-1). ICAM-1 is over-expressed in corneal and conjunctival tissues in dry eye disease. LFA- 1/ICAM-1 interaction contributes to the formation of immunological synapses resulting in T-cell activation and migration to target tissues. Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. This in a market estimated to be worth more than $2.4 billion, one that affects up to 100 million people worldwide, and one that is expected to grow by almost 3% yearly. The US dry eye target market for lifitigrast is estimated at about million patients. Estimated Cost of Therapy: Approx. $250 per month Restasis [cyclosporin drops - Shire (Allergan); Artificial Tear Pipeline Product(s): Restasis X (cyclosporin suspension - Allergan): Phase 3 Comments: FDA acceptance of lifitegrast's resubmission on February 4, 2016 with a Prescription Drug User Fee Act ("PDUFA") date of July 22, lixisenatide (Lyxumia - Sanofi) Current Status: This product is currently under FDA review with an action date likely in late-july Route of Administration/Dosing: Once daily subcutaneous (SQ) injection. Treatment of adults with type 2 diabetes mellitus (T2DM) Lixisenatide is a glucagon-like peptide (GLP) 1 mimetic. Incretins, such as GLP-1, enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut. If approved, lixisenatide would be a once-daily competitor in the GLP1 class of medications for treating type 2 diabetes. In 2012, GLP-1 mimetic drugs generated an estimated $1.5 billion in annual sales. Diabetes affects an estimated 25.8 million people in the U.S. with only about 18.8 million officially diagnosed. Spending on diabetes medications totaled $22 billion in 2012, according to IMS Health. Approximately 90% of individuals have type 2 diabetes. Est. Annual Sales (Millions): $297 Global Sales (2016) Bydureon (exenatide extended-release - AZ); Byetta (exenatide - AZ); Victoza (liraglutide - Novo Nordisk); Tanzeum (albiglutide - GSK); Trulcity (dulaglutide - Lilly) Pipeline Product(s): semaglutide (Novo Nordisk) - Phase 3 (once weekly); semaglutide oral (Novo Nordisk): Phase 2 Comments: Lyxumia is a long-acting glucagon-like peptide-1 (GLP-1) drug for treating type 2 diabetes. GLP-1 levels rise during a meal to help the body utilize and control the elevation in blood sugar levels. It is administered once daily by subcutaneous injection. If approved, this product will compete more closely with oncedaily Victoza. The manufacturer withdrew the original new drug application (NDA) and re-submission was planned for third quarter As a result, this product could be approved mid /29/2015: FDA has accepted for filing the NDA for lixisenatide.

13 lixisenatide / insulin glargine (iglarlixi - Sanofi) Current Status: This product is currently under FDA review with an action date of 06/23/2016 Route of Administration/Dosing: Once daily subcutaneous (SQ) injection Treatment of type 2 diabetes Lantus (insulin glargine) is a long-acting basal insulin, a hormone that prompts the update of glucose into the liver and muscle cells. Lixisenatide is a Glucagon-Like Peptide-1 (GLP-1) analog that helps lower blood glucose levels via several mechanisms, including increasing insulin secretion, decreasing glucagon secretion and delaying gastric emptying slowing glucose absorption. Patients will be able to administer both drugs in a single injection, eliminating the need for two injections per day in some individuals with Type 2 diabetes. Single agents used in combination: long acting basal insluins and GLP-1 analogs Pipeline Product(s): insulin degludec / liraglutide (Xultophy - Novo Nordisk) - PDUFA date of 07/25/2016 Comments: Lixilan (proposed brand name) is a combination of the company's recently approved ultra-long acting insulin, Lantus (insulin glargine), and a GLP-1 analog, lixisenatide. It will likely be used in patients with type 2 diabetes requiring therapy with both agents to control their blood glucose levels. The long acting insulin primarily works by lowering fasting blood glucose levels. The GLP-1 analog helps to control postprandial (after mealtime) blood glucose levels. Therapy with Victoza has also resulted in weight loss, one of the risk factors associated with type 2 diabetes. The lixisenitide/lantus combination is likely to be useful in patients who have gained significant weight on insulin and require a GLP-1 for weight loss. 02/22/ the NDA for LixiLan, the once-daily, fixed-ratio combination of lixisenatide and basal insulin glargine 100 Units/mL, has been accepted for review by FDA. The combination product is an investigational new type of treatment for adults with Type 2 diabetes.05/25/2016 Update: The FDA's Endocrinologic and Metabolic Drugs Advisory Committee votes 12-2 in favor of approval. morphine sulfate e.r. (Arymo ER - Egalet) Current Status: This product is currently under FDA review with an action date of October 14, 2016 Route of Administration/Dosing: Twice daily oral therapy Management of pain severe enough to require daily, around-the-clock opioid treatment and for which alternative treatments are inadequate Abuse-deterrent opioid product containing the opioid analgesic, morphine. Arymo ER would provide another long-acting opioid agonist for treating severe pain. It will compete with available long-acting brand and generic opioid products. Comments: Eagle Pharmaceuticals has submitted a new drug application (NDA) for Arymo ER, an abuse-deterrent, extended-release formulation of morphine sulfate. The company has also submitted data demonstrating bioequivalence of Arymo ER 15, 30 and 60mg to equivalent doses of MS Contin (morphine sulfate controlled-release). Arymo ER is seeking labeling claims to deter abuse via intravenous injection, snorting and oral abuse (crush resistant). Looking forward, as abuse deterrent products become available, legislation and/or FDA may require the use of the abuse deterrent products and/or the removal of the non-abuse deterrent formulations from the market (e.g. Oxycontin - original formulation) in an attempt to help curb the opioid abuse epidemic. Recently, FDA announced a plan will focus on policies that can help reverse the epidemic while continuing to allow patients who are in pain to access effective care. One of the agency's initiatives is to expand access to, and encourage development of, abuse deterrent formulations of opioid products. The NDA was accepted by FDA with an expected review date of October 14, 2016.

14 oxycodone / naltrexone e.r. (Troxyca ER - Pfizer) Current Status: This product is currently under FDA review with an action date in October Approval still pending. Route of Administration/Dosing: An extended-release formulation of a fixed-dose combination of oxycodone (20mg) and naltrexone (2.4mg). The product is administered orally either once or twice daily. Treatment of moderate-to-severe pain, including low back pain Abuse-deterrent opioid product containing a combination of the opioid analgesic oxycodone and opioid antagonist naltrexone. When the formulation is tampered with, oral naltrexone is released and counters the euphoric effects of oxycodone. Another treatment option for treating chronic pain. $7 billion U.S. opioid market. Globally, the pain med market is $50 billion. Est. Annual Sales (Millions): $238 Global Sales (2019) Long acting opioid analgesics, many of which are available as generics. Comments: Pfizer is developing ALALO-02, an extended-release formulation of a fixed-dose combination of oxycodone (20mg) and naltrexone (2.4mg) for the treatment of moderate-to-severe pain. The product consists of pellets with a naltrexone core surrounded by oxycodone, dosed in a capsule. The product is designed to reduce abuse and when the pellets are crushed in an attempt to abuse oxycodone/naltrexone, naltrexone is released and is designed to counter the effects of oxycodone. 06/08/2016: A U.S. advisory panel on Wednesday recommended approval of Pfizer Inc's long-acting opioid painkiller Troxyca ER, saying it dulls pain and its design could deter abuse by addicts in search of a quick high. The panel, however, had reservations about the drug's ability to curb all forms of abuse, voting against a claim that it deters oral abuse while endorsing claims of deterring injecting or snorting the drug. FDA approval is still pending. oxycodone, extended-release (Remoxy - Pfizer) Current Status: This product is currently under FDA review with an action date of Sep. 25, 2016 Route of Administration/Dosing: Oral therapy (twice daily) Twice-daily treatment of moderate to severe pain requiring continuous opioid use for an extended period of time. Abuse-deterrent opioid product containing the opioid analgesic, oxycodone. Another treatment option for treating chronic pain. $7 billion U.S. opioid market. Globally, the pain med market is $50 billion. Est. Annual Sales (Millions): $496 Global Sales (2020) Comments: Remoxy is intended to meet the needs of physicians who appropriately prescribe opioid painkillers and who seek to minimize risks of drug diversion, abuse or accidental patient misuse. Remoxy resists injection or snorting. Published data also show that freezing, crushing or submerging Remoxy in high-proof alcohol for hours at a time releases just a fraction of oxycodone at time points when abusers presumably expect to get high. 03/29/2016 The NDA for Remoxy was resubmitted with a priority review. FDA is expected to rule on the approval of Remoxy by Sep. 25, oxymetazoline 1% topical cream (AG Allergan) Current Status: This product is currently under FDA review with an action date during the first quarter of Route of Administration/Dosing: Topical therapy (once daily) Treatment of persistent facial erythema (redness) associated with rosacea in adults. Oxymetazoline, an alpha 1 and 2 adrenergic agonist, is a potent vasoconstrictor of the cutaneous microvasculature. Rosacea is estimated to affect more than 16 million Americans; Highest Prevalence Among Women, Years Old Antibiotics, anti-acne medications, and Mirvaso (brimonidine 0.33% - Galderma) Comments: Many products are available to treat rosacea, but they primarily treat the papules, the bumps, the pustules but do not effectively treat the redness. As a result, there is an unmet medical need in the treatment of redness. Mirvaso (brimonidine 0.33% - Galderma), an alpha adrenergic agonist, was approved in Aug for the topical treatment of persistent (nontransient) facial erythema of rosacea in adults 18 years of age or older. Allergan's oxymetazoline topical cream will compete directly with Galderma's Mirvaso for market share. However, oxymetazoline topical cream may be associated with a lower rate of adverse events, ultimately resulting in a lower incidence of product discontinuation.

15 solithromycin (CEM101 - Cempra) Current Status: NDA submitted. Estimated PDUFA date is Jan. 3, Priority review anticipated (QIDP product). Route of Administration/Dosing: Oral and Intravenous (IV) therapies Treatment of community acquired bacterial pneumonia (CABP) Solithromycin is a 4th generation oral and intravenous fluoroketolide chemically engineered to evade common mechanisms of macrolide-resistance. CABP (community acquired bacterial pneumonia) is a leading cause of death worldwide. Solithromycin will offer a new treatment option for patients with community acquired bacterial pneumonia (CABP). In the US, there are between 5 to 10 million cases annually, leading to as many as 1.1 million hospitalizations and 45,000 deaths. Est. Annual Sales (Millions): $2,300 Global Sales (Peak) azithromycin and levofloxacin Comments: Solithromycin is expected to file a NDA in the first half of With fast track and priority review, approval will likely occur in the 2nd Half The spectrum of activity of macrolides includes streptococci as well as atypical bacteria such as Mycoplasma and Legionella and intracellular bacteria such as Chlamydia. The guidelines for treating CABP call for use of macrolides as the first line of treatment. The most commonly prescribed antibiotic for this indication is azithromycin with 51 million prescriptions written in the US in This treatment will soon stop being effective due to the increasing level of bacterial resistance to antibiotics. Resistance to azithromycin is reaching 40% of tested bacteria in the US. Azithromycin is also unique in being available in both IV and oral form, which allows doctors to discharge patients for continuing their treatment in the home setting. Once approved, solithromycin is poised to capture share not only in CABP, but also other outpatient respiratory infections where azithromycin (AZ, Z-pack ) is widely prescribed. Approval could occur by the end of 2016 and, the company is planning a 2017 launch. testosterone undecanoate (LPCN Lipocine) Current Status: This product is currently under FDA review with an action date of June 28, 2016 Route of Administration/Dosing: Oral therapy Twice-daily oral formulation of testosterone for replacement therapy in adult men with hypogonadism Testosterone replacement therapy An oral testosterone replacement product would not only be convenient, but would avoid many of the safety issues associated with accidental transfer of testosterone to women or children that can occur from transdermal products. Injectable and topical testosterone. Oral products also available, but less commonly used due to adverse effects. Comments: LPCN1021 is testosterone undecanoate, a prodrug of testosterone formulated for oral administration used for testosterone replacement therapy. The bioavailability of testosterone is low (4-7% in literature). Testosterone undecanoate is a fatty-acid ester prodrug allowing the drug to be absorbed via intestinal lymphatics, reducing first pass hepatic effect. Hydrolysis of the drug occurred by esterases primarily in the blood and liver. Currently available testosterone formulation, methyl testosterone, is reported to have liver safety issues. This product is currently under FDA review with an anticipated June 28, 2016 action date.