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Afrezza usage is different from other RAA - for instance, a few mins into a meal, one or more follow-up dosages, unit conversion. Afrezza needs to be optimally used according to ATA (Different titration) to showcase TIR, TTT which are measurable outcomes to improve insurance coverage.

In a nutshell, Superiority study needs to also incorporate usage. It’s pretty common that different meds have different usages as normally shown on the labels.

The out of control T2 successful Study may potentially reduce some Step Therapy, PA requirements.

Here are the two Superiority Studies.

We anticipate our pediatric program to be Phase III ready by the end of 2019. We also expect a few additional readouts this year from our One Drop study as well as our investigator trial type 2 patients with Dr. Phil Levine in Baltimore.

We’re excited to see the interim analysis presented at the upcoming scientific conferences in 2019.”

Superiority Study:
Initiating Mealtime Ultra-Rapid Acting Insulin (Afrezza) in Uncontrolled Type 2 Diabetes Patients
clinicaltrials.gov/ct2/show/NCT03324776?term=Afrezza&rank=1

Read more: mnkd.proboards.com/thread/10754/mannkind-corporation-hold-investor-conference?page=13#ixzz5e29XkbMY

A Randomized Controlled Trial Evaluating One Drop | Premium With Afrezza vs. One Drop | Premium Alone
clinicaltrials.gov/ct2/show/NCT03313960?term=Afrezza+one+drop&cntry=US&rank=1

“We have been working diligently with our partner in Brazil and regulatory authorities to secure our first approval outside the U.S. and hope to have an update for you on this surely as the holidays slowed down our review unfortunately. We need to finish our part one of our pediatric program to file what is known as a PIP in the EU before we can engage in a meaningful filing application for Europe.

We anticipate filing in Canada in the first half of 2019 and meeting with the European regulatory authorities to start a [indiscernible] over there as these are the two most common places where we get requests for Afrezza from our international inquiries.

We know it takes time to gain regulatory approval in these markets and we’ll make appropriate call to look for one go-to-partner ex-U.S. or continue to find key partners in each market like we did with Brazil and India.”

“We have been working diligently with our partner in Brazil and regulatory authorities to secure our first approval outside the U.S. and hope to have an update for you on this surely as the holidays slowed down our review unfortunately. We need to finish our part one of our pediatric program to file what is known as a PIP in the EU before we can engage in a meaningful filing application for Europe.

We anticipate filing in Canada in the first half of 2019 and meeting with the European regulatory authorities to start a [indiscernible] over there as these are the two most common places where we get requests for Afrezza from our international inquiries.

We know it takes time to gain regulatory approval in these markets and we’ll make appropriate call to look for one go-to-partner ex-U.S. or continue to find key partners in each market like we did with Brazil and India.

We anticipate our pediatric program to be Phase III ready by the end of 2019. We also expect a few additional readouts this year from our One Drop study as well as our investigator trial type 2 patients with Dr. Phil Levine in Baltimore.

We’re excited to see the interim analysis presented at the upcoming scientific conferences in 2019.”

Superiority Study:
Initiating Mealtime Ultra-Rapid Acting Insulin (Afrezza) in Uncontrolled Type 2 Diabetes Patients
clinicaltrials.gov/ct2/show/NCT03324776?term=Afrezza&rank=1

Principal Investigator: Philip Levin, MD Senior Director of MODEL Clinical Research

Primary Outcome Measures :
Percentage change from baseline HbA1c [ Time Frame: 3 months ]
Demonstrate that the addition of mealtime Afrezza can significantly lower HbA1c within 3 months in uncontrolled type 2 diabetes patients initially having HbA1c of 7.5 or higher, despite at least 6 months of prior therapy with diabetes medications.

Secondary Outcome Measures :
Percentage of patients having HbA1c under 7% [ Time Frame: 3 months ]
Demonstrate that the addition of mealtime Afrezza can significantly lower HbA1c within 3 months in uncontrolled type 2 diabetes patients initially having HbA1c of 7.5 or higher, despite at least 6 months of prior therapy with diabetes medications.

Percent of time that Blood glucose (BG) is under 70 mg/dL on CGMS [ Time Frame: 3 months ]
Demonstrate that the addition of mealtime Afrezza can lower blood glucose in uncontrolled type 2 diabetes patients.

A positive outcome could change SOC, Label, results in new favorable publications.

Afrezza Safety and Pharmacokinetics Study in Pediatric Patients
clinicaltrials.gov/ct2/show/NCT02527265?term=Afrezza&rank=5

Pediatric investigation plans (PIP): questions and answers
www.ema.europa.eu/en/human-regulatory/research-development/paediatric-medicines/paediatric-investigation-plans/paediatric-investigation-plans-questions-answers

The milestones related to Trep-T are divided into 6 categories

Milestone A is $12.5 million
Milestone B is $12.5 million
Milestone C is $12.5 million
Milestone D is $12.5 million
Milestone E is $15 million
Milestone F is $15 million

Milestone Payments (A) through (D) shall be made no more than once (and each only upon the first achievement of the corresponding milestone), irrespective of how many Products achieve the corresponding milestone.

Milestone Payments (E) and (F) above may be paid more than once (i.e., if there are multiple Optioned Agents), but each shall be paid only once for the first Optioned Product for each Optioned Agent that reaches the corresponding milestone.

No unachieved Milestone Payments shall accrue and be due if notice has been given by United Therapeutics for termination of the Agreement

seekingalpha.com/article/4218970
A+B+C+D = $50M for Trep-T which may have multiple products.

E+F = $30M per first Optioned Product for each Optioned Agent which may spawn multiple products plus $10M upfront for each Optioned Agent.

MC mentioned $37.5 M over 18 mos refered to A+B+C.

Superiority Study:

A Randomized Controlled Trial Evaluating One Drop | Premium With Afrezza vs. One Drop | Premium Alone
clinicaltrials.gov/ct2/show/NCT03313960?term=Afrezza+one+drop&cntry=US&rank=1

Detailed Description:
Eligible participants (N=400) with an A1c > 7.0% already prescribed a rapid-acting insulin will be randomized to one of two groups: (1) One Drop | Premium 'On Track' (i.e., use the One Drop | Mobile app with in-app diabetes education accredited by the American Diabetes Association with supplemental Afrezza content and a live Certified Diabetes Educator messaging in the app, the 'Chrome' Bluetooth-connected blood glucose meter that uploads blood glucose values in the app, and 150 test strips per month) in combination with Afrezza treatment (n=200) or (2) One Drop | Premium 'On Track' plus their current rapid-acting insulin (n=200).

Primary Outcome Measures :
Hemoglobin A1c [ Time Frame: 3 months ]
3-month between-group change in A1c assessed by a central lab


Secondary Outcome Measures :
Insulin Device Satisfaction [ Time Frame: 3 months ]
Within- and between-group change in insulin device satisfaction assessed by the Insulin Device Satisfaction Survey (IDSS)

Treatment Adherence [ Time Frame: 3 months ]
Within- and between-group change in treatment adherence assessed by the Adherence to Refills and Medications Scale for Diabetes (ARMS-D) and the Summary of Diabetes Self-care Activities Medications Subscale administered for each oral diabetes medication (SDSCA-MS) and insulin in the regimen (SDSCA-IS).

Self-care [ Time Frame: 3 months ]
Within- and between-group change in self-care assessed by the SDSCA's other subscales

Health-related Productivity [ Time Frame: 3 months ]
Within- and between-group change in health-related productivity assessed by the Work Productivity and Activity Impairment measure (WPAI).

Health-related Quality of Life [ Time Frame: 3 months ]
Within- and between-group change in health-related quality of life assessed by the Centers for Disease Control Health-related Quality of Life-14 (CDC HRQOL-14) and life satisfaction assessed by the Cantril Self-Anchoring Ladder of Life Satisfaction.

MC on 12/7/18:
“We are awaiting feedback from Brazil and I have stated Canada could be filed in 1H19. Mexico is not clear bc the administration and rules just changed so once we get an update I will share more.“

We are due for some news anyday now.

www.biopharmadive.com/news/mylans-generic-copaxone-wins-in-court-but-market-barriers-remain/539666/
10/15/2018

The U.S. Court of Appeals for the Federal Circuit last week found Teva's Copaxone 40 mg/mL dosing patents to be "invalid as obvious," supporting previous rulings made by the U.S. District Court for the District of Delaware and the Patent Trial and Appeal Board.

Mylan's 20 mg/mL and 40 mg/mL glatiramer acetate injections, generic versions of Teva's Copaxone, were approved by the Food and Drug Administration in October 2017.

Copaxone, one of the most prescribed treatment for relapsing forms of multiple sclerosis in the U.S., had brand sales of $527 million for the 20 mg/mL dose and $2.86 billion for the 40 mg/mL dose in the year ending August 31, 2018, according to data from IQVIA cited by Mylan.

Teva has been losing share in the U.S. multiple sclerosis market as competition stiffens and generics to Copaxone, such Momenta Pharmaceuticals and Novartis' Glatopa, gain approval.

Generic versions of Copaxone 20 mg have been on the market for several years, but dosing patents helped to protect Teva's 40 mg version until Mylan launched its copy last fall. The appeals court decision helps to cement Mylan's market entry.

[The Inhaled CBD-based DPI compound can really hurt the lucrative Copaxone franchise]

According to the Israeli pharma, Copaxone's second quarter sales from the U.S. nearly halved compared to the same period a year ago, dropping from $843 million to $448 million.

Those declines looks set to continue in the quarters to come, particularly if Mylan's copy gains greater traction.

Copaxone turnover should "continue to drag this year and next year, as we see more generic competition on the product," Teva CEO Kåre Schultz said during the company's earnings call in August.

GWPH opened up their pipeline playbook at 2019 37th Annual J.P. Morgan Healthcare Conference.

ir.gwpharm.com/static-files/1b983943-92da-4e39-8385-02e23fa71bfd

Could the undisclosed compound be treating Epilepsy, MS spasticity, Autism Spectrum Disorder (ASD)?

MC:
“the CBD we aren’t in a position to discuss as it’s the partners decision and we are looking to bring more transparency around the focus of RLS in 2019.”

Read more: mnkd.proboards.com/thread/10797/8-weeks-jan-14?page=5#ixzz5cBgMzDjg

www.receptorlife.com/receptor-life-sciences-announces-senior-leadership

Dr. Devinsky is the Director of the NYU Comprehensive Epilepsy Center and the Saint Barnabas Institute of Neurology and Neurosurgery. He is also a Professor of Neurology, Neurosurgery, Neuroscience and Psychiatry at NYU School of Medicine. In the field of cannabinoid research, He served as the lead investigator for the development of GW Pharmaceuticals' Epidiolex (cannabidiol, or CBD) for the treatment of convulsive seizures in patients with Dravet Syndrome and drop seizures in patients with Lennox-Gastaut syndrome, rare and severe forms of childhood-onset epilepsy. Dr. Devinsky is a recognized authority on the treatment of epilepsy in adults and children.

Significant Unmet Need in Childhood-Onset Epilepsy
• 3.4 million U.S. patients with epilepsy (~470,000 children)
• Approx. 1/3 of patients are pharmacoresistant with seizures persisting despite multiple anti-epileptic drugs (AEDs)
• Multiple distinct orphan syndromes which are highly treatment resistant even with current medications
• LGS and Dravet syndrome represent two of the most difficult-to-treat epilepsy syndromes
RESPONSE TO AEDS IN PATIENTS WITH NEWLY DIAGNOSED EPILEPSY
• ~30-50K with LGS, ~15-20K have Dravet syndrome
• Multipleseizuretypes,developmentaldelay,numerousco-
morbidities
• Seizurescontinueintoadulthood
• Polytherapygenerallyrequired
• Physicians and patients/caregivers seek new treatment options

Epidiolex® Follow-On Indications
Tuberous Sclerosis Complex (TSC)
• Epilepsy is the most common symptom of TSC
• ~25,000patientswithtreatment-resistant
seizures
• Co-morbiditiesinclude:cognitiveimpairment (50%), autism spectrum disorders (<40%), neurobehavioral disorders (> 60%)
• EAP patients with TSC treated with Epidiolex® suggest CBD may be an effective and well- tolerated treatment option
• Single Phase 3 pivotal trial fully enrolled, data expected in 1H 2019
• sNDA planned in 2H 2019

Sativex® for MS Spasticity — Significant Life Cycle Management Opportunity
• Sativex (nabiximols) is an oromucosal spray of a formulated botanical extract of cannabis
that contains the principal cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a 1:1 ratio
• Approved in >25 countries outside of the U.S. for the treatment of spasticity due to multiple sclerosis (MS); sold via marketing partners
• Three positive Phase 3 trials completed in Europe
• U.S. development and commercialization plan
• Evaluating NDA path for MS spasticity
• Potential for multiple indications
• >10 additional placebo-controlled trials completed
• Significant U.S. life cycle management opportunities

CBDV Development Opportunities
Autism Spectrum Disorder (ASD)
• CBDV evaluated in general and syndromic pre-clinical models of ASD yielding promising signals on cognitive and social endpoints,
plus repetitive behavior, 20-patient investigator- initiated EAP study for seizures associated
with autism underway. Initial data on five patients showed:
• Reductionsingeneralizedseizures
• Consistentgainsinsocialengagementand
communication
• Decreased core autism scores
• Investigator-led 100 patient placebo-controlled trial in autism about to commence
• IND filed for a company-sponsored trial in ASD, which we expect to commence in 2019
Rett Syndrome
• Open label study in Rett syndrome and seizures expected in Q1 2019
• CBDV in Rett syndrome has received Orphan Drug Designation from the FDA
Epilepsy
• Currently evaluating next steps for this indication

Additional Pipeline Candidates

Glioblastoma Schizophrenia

• Completed positive Phase 2 study
• THC:CBD + TMZ had an 83% one-year survival rate compared with 44% for patients on placebo (TMZ only) (p=0.042)
• Significantincreaseinmediansurvivalwith CBD:THC; 662 days compared to 369 days on placebo
• Generallywelltolerated
• Orphan Drug Designation from both FDA
and EMA

Schizophrenia

• Novel mechanism distinct from the dopamine D2 receptor augmentation of standard antipsychotics
• Positive top line results from exploratory Phase 2 placebo-controlled clinical trial in 88 patients
• Phase 2B trial under evaluation

Neonatal Hypoxic-Ischemic Encephalopathy

• Intravenous CBD program
• Phase 1 trial complete; Initiating Phase 2 trial
in 2H 2019
• Orphan Drug and Fast Track Designations from FDA and EMA