8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of The Securities Exchange Act of 1934

Date of Report (Date of Earliest Event Reported): January 8, 2018

 

 

Allena Pharmaceuticals, Inc.

(Exact name of registrant as specified in its charter)

 

 

 

DELAWARE   001-38268   45-2729920

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(I.R.S. Employer

Identification No.)

One Newton Executive Park, Suite 202

Newton, Massachusetts

  02462
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code (617) 467-4577

Not Applicable

(Former name or former address, if changed since last report)

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☒

 

 

 


Item 7.01 Regulation FD Disclosure.

Allena Pharmaceuticals, Inc. (the “Company”) will be conducting meetings with investors attending the 36th Annual J.P. Morgan Healthcare Conference in San Francisco beginning on January 8, 2018. As part of these meetings, the Company will deliver the slide presentation furnished to this report as Exhibit 99.1 and which is incorporated herein by reference.

The information in this report furnished pursuant to Item 7.01 shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section. It may only be incorporated by reference in another filing under the Exchange Act or the Securities Act of 1933, as amended, if such subsequent filing specifically references the information furnished pursuant to Item 7.01 of this report.

 

Item 9.01. Financial Statements and Exhibits.

(d) Exhibits

 

Exhibit
No.

  

Description

99.1    Investor presentation furnished by Allena Pharmaceuticals, Inc. on January 8, 2018


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: January 8, 2018     Allena Pharmaceuticals, Inc.
    By:  

/s/ Edward Wholihan

      Edward Wholihan
      Chief Financial Officer
EX-99.1

Slide 1

Bringing First-in-Class Oral Enzyme Therapeutics to Patients with Rare and Severe Metabolic and Kidney Disorders January 2018 Exhibit 99.1


Slide 2

Allena Pharmaceuticals, Inc. These slides contain forward-looking statements and information. The use of words such as “may,” “might,” “will,” “should,” “expect,” “plan,” “anticipate,” “believe,” “estimate,” “project,” “intend,” “future,” “potential,” or “continue,” and other similar expressions are intended to identify forward-looking statements. All forward-looking statements are based on estimates and assumptions by our management that, although we believe them to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that we expected. These statements are also subject to a number of material risks and uncertainties that are described under the heading “Risk Factors” in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2017 filed with the Securities and Exchange Commission on December 14, 2017, as well as discussions of potential risks, uncertainties and other important factors in our subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.


Slide 3

2017 Accomplishments Position Allena for Catalyst-Rich 2018 …WITH IMPORTANT UPCOMING VALUE DRIVERS IN 2018 SIGNIFICANT MILESTONES ACHIEVED IN 2017 Completed robust Phase 2 clinical program, demonstrating substantial reduction of UOx excretion in patients with enteric hyperoxaluria Prepared to start Phase 3 program for ALLN-177 in enteric hyperoxaluria Presented final data from Phase 2 trials of ALLN-177 at ASN Received orphan drug designation from FDA and European Commission for ALLN-177 in primary hyperoxaluria, presented supporting data at ASN 2017 Initiated preclinical study evaluating ALLN-346 in animal models of hyperuricemia and CKD Raised $75M in successful initial public offering 1Q18 Initiate Study 301, a Phase 3 trial evaluating ALLN-177 in enteric hyperoxaluria 1Q18 Initiate Study 206, a Phase 2 trial evaluating ALLN-177 in patients with primary or enteric hyperoxaluria and hyperoxalemia (systemic oxalosis) 2H18 Initiate Study 302, a Phase 3 trial evaluating ALLN-177 in enteric hyperoxaluria 2H18 Interim data from Study 206 2018 Continue progressing preclinical development of ALLN-346 to support 1H19 IND filing


Slide 4

Investment Highlights Significant Unmet Need in Oxalate and Urate Disorders Late-Stage Development Candidate: ALLN-177 Pioneering Expertise in Oral Enzyme Therapeutics Focused on rare and severe metabolic disorders that can cause kidney stones, damage the kidney, and potentially lead to CKD and ESRD No approved oxalate therapies; potential untapped multi-billion dollar market First-in-class, oral therapy for severe hyperoxaluria Robust Phase 2 program completed: patient population, dosing regimen, trial design, and proposed endpoints identified for pivotal phase 3 program Expect to initiate Phase 3 program in enteric hyperoxaluria and Phase 2 program in other severe and orphan indications in 1Q18 Approach enables treatment of metabolic diseases with oral, non-absorbed enzyme therapeutics GI MOA reduces subsequent metabolic burden on the kidney Raised $75M in successful initial public offering in 4Q17 The company was founded in 2011 with Frazier Healthcare Partners, Third Rock Ventures, and Bessemer Venture Partners. Additional private financing from HBM, Pharmstandard International, Partner Fund, Fidelity Management & Research Company Strong Support from Leading Biotechnology Investors


Slide 5

Product Indication Discovery Pre-Clinical Phase 1 Phase 2 Phase 3 Next Milestone Commercial Rights ALLN-177 Enteric hyperoxaluria Q1 ’18: Initiate Phase 3 program Worldwide Systemic oxalosis* Q1 ’18: Initiate Phase 2 program Worldwide Primary hyperoxaluria* (Orphan Designation) Q1 ’18: Initiate Phase 2 program Worldwide Pediatric hyperoxaluria* (Orphan Designation) Q1 ’18: Initiate Phase 2 program Worldwide ALLN-346 Hyperuricemia and CKD Q4 ’17: Initiate animal POC study Worldwide Allena’s Pipeline: First-in-Class Therapeutic Strategy for Oxalate and Urate Disorders * To be evaluated in a single Phase 2 clinical trial with a basket design that will enroll subsets of patients suffering from complications of severe hyperoxaluria, including adolescents and adults with primary hyperoxaluria or severe forms of secondary hyperoxaluria, both of which can lead to systemic oxalosis.


Slide 6

Hyperoxaluria is characterized by markedly elevated urinary oxalate levels Oxalate is a Metabolite that is Nephrotoxic at High Concentrations Source: Illustration adapted from Coe, Fred. “Control of Urine Oxalate Excretion.” Kidneystones.uchicago.edu. University of Chicago, http://kidneystones.uchicago.edu/control-of-urine-oxalate-excretion/. March 2017. Fecal Excretion Oxalate Absorbed Secreted Filtered Gastrointestinal Tract Oxalate is absorbed and secreted along the GI tract Urinary Excretion Kidney Impairment Kidney is unable to filter (declining eGFR) Oxalate is measured in plasma Kidney Stones Excreted or removed Oxalate is measured in the urine Kidney Damage and Inflammation Crystal deposition in parenchyma Foods Oxalate rich foods Liver Endogenously produced oxalate ALLN-177 targets and degrades oxalate along the GI tract


Slide 7

First-in-Class Therapeutic Strategy Expertise and Proprietary Technological Approach in Enzyme Therapeutics Enables First-in-Class Therapeutic Strategy for Oxalate and Urate Disorders ALLN-177 Recombinant Protein Oral, non-absorbed, highly specific Optimized Highly Active Form of the Enzyme for GI Tract Stabilize enzyme without compromising activity Streamlined, Robust Manufacturing COGS in the range of oral small molecules Clinical Trial Materials Ready to Start Phase 3 Convenient, 1-2 capsules per meal RT-stable formulation Oral enzymes designed to rapidly degrade a specific metabolite within the gut, reducing GI absorption and accumulation in the kidney, blood and other organ systems


Slide 8

Gastric bypass surgery Crohn’s disease Short bowel syndrome Cystic fibrosis EH patients are diagnosed and treated by nephrologists and urologists often in Stone Clinics in academic and community settings High unmet need: more frequent and more complex stones; fail standard of care (i.e., hydration, dietary modifications) EH patients in Allena’s clinical program: Very high baseline UOx >94% of EH subjects in 713 had experienced at least one kidney stone with an average of >3 kidney stones visible by routine CT scan Stones and CKD burden - $66K average annual direct expenditures 4 years post GI malabsorptive procedure or disease diagnosis Pancreatic insufficiency Celiac disease Liver disease Ulcerative Colitis There are no FDA approved pharmacological therapies to treat any form of hyperoxaluria Primary hyperoxaluria: Orphan genetic disorder caused by endogenous over production of oxalate in the liver Enteric Hyperoxaluria Patients are a High Risk Patient Population who are Identifiable by Physicians and Need Treatment Enteric Hyperoxaluria (EH) Urinary Oxalate (UOx) Secondary hyperoxaluria: Disorder caused by hyperabsorption of oxalate in the GI tract Enteric: due to underlying GI disorders Idiopathic: due to an unknown cause Idiopathic and Kidney Stone Disease ~5M Enteric ~200K– 250K ~5K Primary


Slide 9

ALLN-177 Initially Targets Enteric Hyperoxaluria Patients with Underlying Malabsorptive GI Diseases and Kidney Stones 1 Truvan Health Analytics, part of the IBM Watson Health business longitudinal Claims Analysis, August 2017. Analysis tracked patients for whom an enteric disease diagnosis or procedure code was entered between 7/1/10 - 6/30/12 who did not have a claim with an KSD, CKD/ESRD/Dialysis diagnosis or procedure code from 1/1/10 - 6/30/10. Analysis showed that approximately 5% of patients subsequently developed one or more kidney stones (“Kidney Stone Disease"), of which 40% also developed CKD over the subsequent four years to determine prevalence in 2012. 2017 figures apply 3.6% CAGR to 2012 population figures. Approximately 9% of patients develop CKD without kidney stone disease within 4 years 4.4 Million Estimated Patients with GI Malabsorptive Conditions with no Prior Kidney Stones or CKD 200-250K Estimated Patients with Enteric Hyperoxaluria and Kidney Stones 4 year progression of disease Kidney stones, often the first clinical manifestation of hyperoxaluria, allow patients to be identified Patients Potentially at Risk for Enteric Hyperoxaluria1 Patients developed Kidney Stone Disease of which 40% developed CKD ~2017 US population impacted by stones and enteric hyperoxaluria ~5%


Slide 10

Risk of Renal Complications Rises with Higher Urinary Oxalate Levels: Reduction of UOx Improves Renal Outcomes Illustrative Diagram Sources: Robertson and Hughes, Scanning Microsc. 1993; Keddis Curr Opin Nephrol Hypertens. 2013; Robertson and Peacock, Nephron. 1980; Milliner, Kidney Int. 2006; Curhan and Taylor, Kidney Int. 2008; Milliner, Clin J Am Soc Nephrol. 2015. Key Studies: Borghi N Eng J Med. 2002; Taylor and Curhan, J Am Soc Nephrol. 2007; Milliner, N Eng J Med 1994 and Lieske JASN Abstract Supplement 2017 Urinary Oxalate Literature and KOL Input: ~20% reduction in UOx would be clinically meaningful Key Peer Review Studies: Higher baseline UOx predicts future stone events in enteric hyperoxaluria patients (Lieske ASN 2017) 50% reduction in risk of kidney stone recurrence associated with >20% decrease in UOx (Borghi 2002) 25-50% reduction in kidney stone recurrence rate associated with >20% decrease in UOx (Curhan and Taylor 2008) Preservation of renal function associated with ~10% reduction in UOx (Milliner 1994) Urinary Oxalate (UOx) mg/24h Kidney Damage 102030405060708090100>100 Kidney Failure Normal Kidney Function Kidney Stones CaOx Crystal Formation Systemic Crystal Deposition Risk of Kidney Complications* Increasing Severity ALLN-177 Mechanism of Action * The complications noted in the figure represent a general progression of kidney harm and disease associated with increasing urinary oxalate excretion levels. Not all patients experience this progression and there is considerable variability among individuals between urinary oxalate excretion levels and kidney function and disease. Idiopathic Hyperoxaluria Enteric Hyperoxaluria Primary Hyperoxaluria Normal


Slide 11

Kidney Week Highlights: Increasing Awareness of Oxalate Disorders Silent Hyperoxaluria Contributes to CKD Progression in a Patient with Short Bowel4 Oxalate Nephropathy Leading to ESRD Following Roux-en-Y Gastric Bypass5 Oxalate Nephropathy: A Case of Acute Renal Failure from Chronic Pancreatitis6 The Association of Calcium Oxalate Deposition in Kidney Allografts with Graft and Patient Survival7 Results of a Phase 2 RCT of ALLN-177 in Patients with Secondary Hyperoxaluria8 Clinical Characteristics and Tolerability of ALLN-177 in Phase 2 Studies of Patients with Secondary Hyperoxaluria9 ALLN-177, a Novel Oral Enzyme Therapy, Reduces Urinary Oxalate Excretion and Plasma Oxalate in Porcine Dietary Model of Severe Hyperoxaluria10 Urinary Stone Events are Predicted by Urinary Oxalate Excretion in Enteric Hyperoxaluria1 Relative Supersaturation of 24-hr Urine and Likelihood of Kidney Stones2 Absolute Compared with Percentage Differences in 24-Hour Urine Oxalate and Likelihood of Being a Kidney Stone Former3 Increasing UOx Increases Risk of Kidney Stone Formation Oxalate Progressively Damages the Kidney ALLN-177 Reduced UOx in Phase 2 Clinical Study 1 D’Costa MR et al. J Am Soc Nephrol 28, 2017:380. 2 Prochaska M et al. J Am Soc Nephrol 28, 2017:381. 3 Curhan GC et al. J Am Soc Nephrol 28, 2017:381. 4 Vela-Ortiz MC et al. J Am Soc Nephrol 28, 2017:1119. 5 Drury E et al. J Am Soc Nephrol 28, 2017:1122. 6 Smith TR et al. J Am Soc Nephrol 28, 2017:1131. 7 Palsson R et al. J Am Soc Nephrol 28, 2017:356. 8 Nigwekar SU et al. J Am Soc Nephrol 28, 2017:380. 9 Nigwekar SU et al. J Am Soc Nephrol 28, 2017:1113. 10 Grujic D et al. J Am Soc Nephrol 28, 2017:380.


Slide 12

ALLN-177 for the Treatment of Hyperoxaluria


Slide 13

Clinical and Regulatory Progression of ALLN-177 Pre clinical Ph 1 Healthy Volunteers Ph 2 Open Label Ph 2 Randomized Controlled ✓ ✓ ✓ ✓ Porcine Rhubarb Model Presented at AUA 2016 Progressive Increase in Enzyme Activity Porcine Western Diet Model Presented at ASN 2016 n=30 A Double Blind, Placebo Controlled, Randomized Cross-Over Study with ALLN-177, an Orally Administered Oxalate Degrading Enzyme Langman et al, Am. J Nephrol 2016;44:150-158 Presented at ASN 2014 n=16 Multicenter, Open Label, Single Arm Outpatient Study in Enteric and Idiopathic Hyperoxaluria Presented at ASN 2015 n= 67 649: Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Crossover in Enteric and Idiopathic Hyperoxaluria 713: Multi-Center, Randomized, Double-Blind, Placebo-Controlled in Enteric and Idiopathic Hyperoxaluria Presented at ASN 2017 2° Hyperoxaluria 1° Hyperoxaluria Pre clinical Orphan Designation Initiating Ph 2 Study ✓ ✓ Q1 2018 AGTKO Mouse Model Grujic et al, Am. J Nephrol 2009; 29: 86-93 Porcine Dietary Hydroxyproline and Porcine Sodium ox-IV injection model FDA grants Orphan Disease Designation for ALLN-177 in both PH and Pediatric Hyperoxaluria (Primary and Secondary) EC grants Orphan Disease Designation for ALLN-177 in PH Clinical Trial in Patients with Primary or Enteric Hyperoxaluria Patients and Hyperoxalemia CT.GOV: NCT03391804


Slide 14

Goals Results Robust Phase 2 Program Leads to Phase 3 Strategy for ALLN-177 Phase 3 Phase 2 Program Phase 1 Open Label 396 Study: Demonstrated POC in kidney stone patients with hyperoxaluria (n=16; 5 EH) Adaptive 649 Study: Tested cross over design and multiple doses (n= 30; 8 EH) Parallel 713 Study: Treated patients for 28 day duration in potential Phase 3 prototype (n=67; 18 EH) Pilot Study 204 Oxalate Absorption Challenge: Tested patients for oxalate hyperabsorption (n=22; 5 EH) Healthy Volunteer Study: Established POC Study 713 - Largest RCT of Novel Therapeutic for Oxalate Diseases: Identified Proposed Phase 3 Patient Population Enteric population demonstrated consistent, superior, clinically and statistically significant response Identified Proposed Pivotal Endpoint Mean change from baseline to time-weighted average UOx excretion/24h: we believe most appropriate endpoint because it reflects benefit of metabolic control of UOx excretion over time Identified Proposed Phase 3 Trial Design Parallel, RCT vs placebo optimal design, dosing up to 5x per day per meal or snack ü ü ü


Slide 15

ALLN-177 n=32 Placebo n=35 Enteric ALLN-177 n=11 Enteric Placebo n=7 Baseline urinary oxalate (mg/24h) 71.81 (41.35) 66.81 (38.22) 104.39 (56.04) 101.54 (70.42) Study 713: Study Design and Baseline Characteristics Sources: Taylor et al. Oxalate Intake and the Risk for Nephrolithiasis. J Am Soc Nephrol. 2007, Holmes et al. Contribution of Dietary Oxalate to Urinary Oxalate Excretion. Kidney Int. 2001  All subjects receiving standard of care (i.e., hydration, dietary modifications) On average, subjects with EH had baseline 103 mg/24 hour and idiopathic subjects 57mg/24 hour EH baseline UOx almost 2X higher than idiopathic patients despite oxalate consumption being two fold lower Enteric Hyperoxaluria (EH) Urinary Oxalate (UOx) Placebo ALLN-177 Screening Randomization Usual diet plus ALLN-177 (7,500 u) or placebo TID with meals x 28 days Baseline 3 days Follow up 1 week UOx>50mg/24h eGFR ≥45 Objective: Evaluate safety and efficacy of ALLN-177 vs placebo over 28 days' treatment 1:1 2 UOx 1 UOx 1 UOx 3 UOx 2 UOx Week 1 Week 2 Week 3 Week 4 TWA UOx: Based on the average of all UOx measurements obtained during Weeks 1-4, with each value weighted for the number of data since the last urine collection. Baseline Number of Urine Oxalate (UOx) Collections (mg/24hr)


Slide 16

Study 713: Substantial Treatment Effect in Pre-specified Enteric Hyperoxaluria Population from Baseline to TWA Across 4 Weeks vs Placebo UOx: Urinary oxalate excretion (mg/24 h) LS means, LS differences (treatment – placebo), 90% confidence intervals and one-sided p-values are obtained from the MMRM model with treatment, week, treatment by variable. Overall (n=67) Enteric (n=18) Absolute Change Endpoint ALLN-177 vs placebo (∆) p-value ALLN-177 vs. placebo (∆) p-value Change in UOx (mg/24h) from baseline to Week 4 10 -6.35 mg/24h 0.160 -16.45 mg/24h 0.184 Change in UOx (mg/24h) from baseline to TWA across 4 weeks 20 -8.13mg/24h 0.016 -25.69 mg/24h 0.018 Percent Change Percent change in UOx from baseline to Week 4 20 -15.81% 0.016 -36.25% 0.046 Percent change in UOx from baseline to TWA across 4 weeks Post-Hoc -14.23% 0.015 -39.15% 0.010 Proportional Analysis Proportion of subjects with ≥ 20% decrease in UOx from baseline to TWA across 4 weeks Post-Hoc 40.6% vs. 8.6% 0.006 63.6% vs. 14.3% 0.092


Slide 17

Substantially Greater ALLN-177 Treatment Response in Enteric Population Provides Design Space for Phase 3 Program Beyond the primary endpoint analysis, all P-values are descriptive. Enteric ALLN-177 Enteric Placebo Change in TWA Urinary Oxalate (mg/24h) Baseline Urinary Oxalate (mg/24h) Change in TWA UOx Excretion vs Baseline UOx Excretion Responder Analysis: Proportion of Patients with Reduction in TWA UOx Excretion (%) Create table Reduction in TWA UOx (%) -10 -20 -30 -40 -50 Enteric ALLN-177 73 64 36 18 9 Enteric Placebo 29 14 0 0 0 ∆ = (8.13) mg/24h *p = 0.016 ∆ = (25.69) mg/24h *p = 0.018 LS Mean UOx Change in TWA (mg/24h) Overall Enteric n ALLN-177 n Placebo


Slide 18

Enteric Patients Also Demonstrated Differential Treatment Effect in 4 Day Open Label Study 396 Mean UOx Change from Baseline n=16 n=5 Baseline (mg/24h) Change in UOx from Baseline (mg/24h) Change in UOx from Baseline (mg/24h) Change in UOx Excretion vs Baseline UOx Excretion


Slide 19

ALLN-177 Generally Well-Tolerated in Clinical Trials to Date 11,500 u/meal, 3,000 u/meal, and 7,500 u/meal. 2TEAE = Treatment emergent adverse events are defined as AEs with onset at the time of or following the first dose of treatment with study drug through 7 days after their last dose of study medication, or AEs starting before the start of treatment but increasing in severity or relationship at the time of or following the start of treatment through 7 days after their last dose of study medication. 3One subject reported congestive heart failure of moderate severity, considered not related to study drug, but secondary to a recent cardioversion for atrial fibrillation. This resulted in hospitalization and withdrawal from the study; same subject in both rows. 4Two placebo treated subjects withdrew from study drug, one after nearly 4 weeks of treatment due to nausea, considered not related, and another due to hives/dermatitis with onset 3 days after starting placebo, considered possibly related. Study 396 Study 649 Study 713 All (n=16) ALLN-1771 (n=30) Placebo (n=24) ALLN-177 (n=32) Placebo (n=35) n (%) n (%) n (%) n (%) n (%) TEAE2 9 (56.3%) 13 (43.3%) 6 (25.0%) 16 (50%) 22 (62.9%) Severe TEAE 0 0 0 0 0 Related TEAE 2 (12.5%) 5 (16.7%) 2 (8.3%) 3 (9.4%) 8 (22.9%) Serious AE (SAE) 0 1 (3.3%)3 0 0 0 Related SAEs 0 0 0 0 0 AEs Leading to Study Drug Withdrawal 0 1 (3.3%)3 0 0 2 (5.7%)4 AEs Leading to Death 0 0 0 0 0


Slide 20

Completed Robust Phase 2 Clinical Program Identified Proposed Phase 3 Patient Population Substantially reduced UOx in patients with EH, a high-risk population Well tolerated, with no drug-related serious or severe adverse events Specific to oxalate, with minimal to no changes in non-oxalate urine parameters EH patients often eat frequent, smaller meals – consumed 28% of their total daily oxalate from snacks Identified Proposed Pivotal Endpoint Mean change from baseline to TWA UOx excretion/24h: we believe most appropriate endpoint because it reflects benefit of metabolic control of UOx excretion over time TWA less sensitive to variability Identified Proposed Phase 3 Trial Design Parallel, RCT vs. placebo optimal design ü ü ü


Slide 21

1H 2017 2H 2017 1H 2018 2H 2018 1H 2019 2H 2019 1H 2020 2H 2020 1H 2021 ALLN-177: Proposed Pivotal Phase 3 Program in Enteric Hyperoxaluria Proposed Phase 3 Program – in Discussions with the FDA: 301: Primary endpoint – TWA UOx weeks 1-4 302: Primary endpoint – TWA UOx weeks 1-4, 24 weeks plus follow-up Pivotal Program: ~525 patients Estimates for Phase 3 Program for Full or Accelerated Approval EOP2 EU Reg advice 302 in Enteric HO, RCT ≈ 24 weeks n=~400 301 in Enteric HO RCT x 4 weeks n=~125 Follow-up (in discussion)


Slide 22

Key Points of General FDA Alignment for the Registrational Program: Change in TWA UOx levels potentially approvable endpoint Dosing up to 5x day with meals and snacks Phase 2 program in secondary hyperoxaluria supports Phase 3 program in enteric hyperoxaluria Enteric hyperoxaluria is a rare disease without available treatment Size of pivotal program (~525 patients) Nonclinical program for ALLN-177 completed Points of Active Discussion: Full vs. accelerated approval Magnitude of effect of reduction of UOx Primary and secondary endpoints ALLN-177 Clinical and Regulatory Update Allena expects to initiate the first of two planned pivotal Phase 3 clinical trials for ALLN-177 in enteric hyperoxaluria in the first quarter of 2018. We are in active dialogue with the FDA to finalize the design of the registrational program. Green light from FDA on design of Phase 2 Study 206 in severe hyperoxaluria, which will start Q1 2018.


Slide 23

Additional ALLN-177 Regulatory Highlights Public-private partnership by the American Society of Nephrology in collaboration with stakeholders in the renal community including the FDA The Kidney Health Initiative recently endorsed a project to bring together patients, clinicians, industry and the FDA to evaluate potential endpoints for future clinical trials in primary and enteric hyperoxaluria: Project titled “Identification of Appropriate Endpoints for Clinical Trials in Hyperoxaluria” Led by the Mayo Clinic in coordination with the Oxalosis and Hyperoxaluria Foundation Mayo Clinic data presented at ASN 2017 Productive meetings held with several countries in Europe for National Scientific Advice on the registrational program General alignment on the proposed regulatory approach European Commission granted orphan designation to ALLN-177 for treatment of primary hyperoxaluria (ASN, FDA, OHF)


Slide 24

Recent Metabolic and Rare Disease Products Have Been Registered on the Basis of Biochemical Endpoints Source: www.accessdata.fda.gov/scripts/cder/daf/index.cfm Uremic Toxin Product Biochemical Endpoint for FDA Approval Measurement Phosphate Ferric citrate Changes in serum phosphorous from baseline (week 52) to week 56 or last measurement (52 week active control and 4 week extension to placebo-control) Primary assessment compared week 52 to week 56 (also measured at weeks 12, 24, 36, 48, 52 and 56 weeks) Potassium Patiromer Changes in mean serum potassium from baseline to week 4 Proportion achieving 3.8-5.0 mEq/L at week 4 Measured serum potassium weekly starting on day 3 for weeks 1, 2, 3 to end of 4 week treatment Uric Acid Lesinurad Proportion of subjects with serum uric acid <6.0 mg/dL by month 6 Measured serum uric acid monthly Parathyroid Hormone Calcifediol Proportion of subjects decrease in plasma intact parathyroid hormone between baseline and end of trial (average of weeks 20, 22, 24 and 26) Measured plasma intact parathyroid hormone biweekly from point 0 to 24 weeks Severe/Rare Disease Product Biochemical Endpoint for FDA Approval Measurement Uric Acid Pegloticase Proportion of subjects maintaining a plasma uric acid <6 mg/dL for at least 80% of the time during month 3 and month 6 Measured plasma uric acid at weeks 13 and 26 Primary Biliary Cirrhosis  Obeticholic acid  The primary endpoint was a responder analysis at Month 12, where response was defined as a composite of three criteria: ALP less than 1.67-times the ULN, total bilirubin less than or equal to ULN, and an ALP decrease of at least 15%  Alkaline phosphatase (ALP) and bilirubin measurements at week 2 and months 3, 6, 9 and 12


Slide 25

ALLN-177 Additional Indications


Slide 26

ALLN-177 has the Potential to Reduce Plasma Oxalate in Severe Enteric and Primary Hyperoxaluria Patients with Hyperoxalemia *Pigs not colonized with oxalobacter formigenes. Sources: Company data, Health Advances Allena Market Strategy February 2017. Zh. ALLN-177 Therapy Degraded Oxalate in the GI Tract and Prevented Plasma Oxalate Increase in Porcine Model In porcine model, ALLN-177 reduced plasma 30% and urinary oxalate 35% after 7 days of treatment with ALLN-177. Oral therapy of 22,500 u/day normalized both plasma and urine oxalate.* Unmet Need: Severe Enteric and Primary Hyperoxaluria patients have elevated levels of plasma oxalate (Hyperoxalemia) due to declining kidney function Frequent hemodialysis (6-7 times per week) alone is not sufficient in this population Oxalate can cause significant damage to the kidney allograft (post transplantation) and other organ systems Animal POC Data Presented at ASN 2017


Slide 27

Screening and Baseline 28 d Follow up 4 Weeks Phase 2 'Basket' Study: ALLN-177 Treatment of Adult and Pediatric Patients with Enteric or Primary Hyperoxaluria and Hyperoxalemia Primary Hyperoxaluria (PH) Enteric Hyperoxaluria (EH) Urinary Oxalate (UOx) Plasma Oxalate (POx) Regulatory: ALLN-177 has been granted separate orphan designations for primary hyperoxaluria and pediatric hyperoxaluria Study Initiation: 1Q18 (CT.GOV: NCT03391804) Hypothesis: By degrading oxalate within the GI tract, ALLN-177 is designed to reduce plasma and urinary oxalate levels in patients with PH or EH and hyperoxalemia. Reduction in plasma oxalate levels (POx) should lead to decreased systemic oxalate deposition (systemic oxalosis). Study Design: Uncontrolled, Open-label Key Endpoints: Change from baseline in POx and UOx Enroll subjects ≥12 yrs of age in both PH and EH Patient population: Primary hyperoxaluria or enteric hyperoxaluria with systemic manifestations of disease Study Aim: Evaluate effect of ALLN-177 in reducing plasma and UOx in patients with primary or enteric hyperoxaluria and hyperoxalemia 1 x POx 2 x 24h n ≈ up to 20 ≥ 12 years PH and EH UOx ≥ 40mg/24hr POx > 5 µmol/L eGFR < 45 mL/minute/1.73 m2 2 x POx 2 x 24h 1 x POx 2 x 24h 1 x POx 2 x 24h 1 x POx 2 x 24h ALLN 2 caps per meal/snack up to 5 x/day (max 10/d) Treatment x 12 Weeks Week 8 Week 12 Week 4


Slide 28

ALLN-346: Significant Opportunity in Gout Patients with Moderate-to-Severe CKD The Gout Market is Incompletely Served by Existing Therapies ~375,000 gout patients with moderate to severe CKD who have uncontrolled gout on urate lowering therapy (ULT) Gout patients with renal impairment are not well managed due to safety concerns for existing therapies Gout patients with kidney and liver problems are contraindicated for allopurinol, Uloric, and Zurampic Current ULT’s may interact with other medications Co-morbidities (e.g. cardiovascular) may also limit ULT options Significant unmet need for safe and effective therapy that can be used in patients with renal impairment Sources: . Lim JJ, Fu AC, and Reasner D. Prevalence of CKD and Uncontrolled Gout Among US Adults: Results from NHANES 2007-2012. Poster presented at: The National Kidney Foundation Spring Clinical Meetings; April 18-22, 2017; Orlando Florida. Fletcher Spaght Analysis July 2016; Image: Retailleau, P., Colloc'h, N., Vivares, D., Bonnete, F., Castro, B., El Hajji, M., Prange, T. (2005) Urate oxidase from Aspergillus flavus: new crystal-packing contacts in relation to the content of the active site. Acta Crystallogr.,Sect.D, 61, 218-229; D. Grujic Urol Res 2008, 193. ALLN-346 Therapeutic Strategy: Novel recombinant urate oxidase MOA: Non-absorbed oral enzyme degrades urate in the GI tract Previous animal data using an unmodified urate oxidase demonstrated normalization of plasma uric acid similar to allopurinol


Slide 29

Forecasted Clinical and Regulatory Milestones 2018 1Q18 Initiate Study 301 in Enteric Hyperoxaluria 1Q18 Initiate Study 206 in Primary or Enteric Hyperoxaluria and Hyperoxalemia 2H18 Initiate Study 302 in Enteric Hyperoxaluria 2H18 Interim Data in Study 206 2019 1H19 File IND for ALLN-346 in Hyperuricemia and CKD 1H19 Additional Data in Study 206 2H19 Topline Data in Study 301 2H19 Topline Data in Study 206 2020 2H20 Phase 3 Results


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Investment Highlights Significant Unmet Need in Oxalate and Urate Disorders Late-Stage Development Candidate: ALLN-177 Pioneering Expertise in Oral Enzyme Therapeutics Focused on rare and severe metabolic disorders that can cause kidney stones, damage the kidney, and potentially lead to CKD and ESRD No approved oxalate therapies; potential untapped multi-billion dollar market First-in-class, oral therapy for severe hyperoxaluria Robust Phase 2 program completed: patient population, dosing regimen, trial design, and proposed endpoints identified for pivotal phase 3 program Expect to initiate Phase 3 program in enteric hyperoxaluria and Phase 2 program in other severe and orphan indications in 1Q18 Approach enables treatment of metabolic diseases with oral, non-absorbed enzyme therapeutics GI MOA reduces subsequent metabolic burden on the kidney Raised $75M in successful initial public offering in 4Q17 The company was founded in 2011 with Frazier Healthcare Partners, Third Rock Ventures, and Bessemer Venture Partners. Additional private financing from HBM, Pharmstandard International, Partner Fund, Fidelity Management & Research Company Strong Support from Leading Biotechnology Investors