Biodel (BIOD) Positive Results Clinical Study Ultra-Rapid-Acting Insulin Analog Candidates

• BIOD-238 and BIOD-250 demonstrate a pharmacokinetic profile superior to Humalog^® with ultra-rapid absorption and rapid declines from peak concentration
• BIOD-250 demonstrates injection site toleration comparable to Humalog^®

DANBURY, Conn., Jan. 24, 2013 (GLOBE NEWSWIRE) — Biodel Inc. (Nasdaq:BIOD) today announced positive top-line results from a Phase 1 clinical trial of two ultra-rapid-acting insulin analog-based formulations, BIOD-238 and BIOD-250, conducted to evaluate the pharmacokinetic and injection site toleration profiles relative to Humalog^®, a rapid-acting insulin analog. BIOD-238 and BIOD-250 are combinations of Biodel’s proprietary excipients with the marketed formulation of Humalog^®.

The single-center, randomized, double-blind, three-period crossover trial in 12 patients with Type 1 diabetes was conducted in Australia. Each study drug was administered subcutaneously on separate days. Pharmacokinetic measurements were made using an assay to quantify the active ingredients in the study drugs and Humalog^®. The clinical trial was powered to measure differences in time to half-maximal insulin concentrations. The hypothesis tested in this study was than Biodel’s formulations of Humalog^® would have ultra-rapid absorption profiles with comparable declines from peak concentration and comparable injection site tolerability profiles relative to Humalog^®. Two approaches were taken to mitigate injection site discomfort—reducing disodium EDTA concentrations (BIOD-238) and addition of magnesium sulfate (BIOD-250), which was observed to improve toleration in a previous study.

The pharmacokinetic profiles of BIOD-238 and BIOD-250 proved to be consistent with our target product profile for analog-based ultra-rapid-acting insulin. Absorption rates of BIOD-238 and BIOD-250 were significantly more rapid than that of Humalog^®, as indicated by 35-45% reductions in mean times to half maximal insulin concentrations (p<0.001 for BIOD-238 and p=0.001 for BIOD-250 vs. Humalog^®) and time to maximal insulin concentrations (p=0.013 for BIOD-238 and p=0.025 for BIOD-250 vs. Humalog^®). Furthermore, the total amount of insulin absorbed over the first 30 minutes following injection of BIOD-238 and BIOD-250 was approximately double that seen for Humalog^® (p<0.001 for BIOD-238 and p=0.002 for BIOD-250 vs. Humalog^®). The decline from peak concentration, as indicated by time to half maximal concentration after the peak, was significantly shorter for both BIOD-238 and BIOD-250 compared to Humalog^® (p=0.009 for BIOD-238 and p=0.016 for BIOD-250 vs. Humalog^®).

Local injection site discomfort was measured with a 100 mm visual analog scale (VAS) and patient questionnaires. 100 mm is defined as the worst possible discomfort and 0 mm is defined a having no discomfort. In the trial, the VAS score was numerically lower, but not significantly different for BIOD-250 compared to Humalog^® (mean VAS scores of 2.7 mm and 8.2 mm for BIOD-238 and Humalog^®, respectively; p=NS). The VAS score for BIOD-238 was significantly higher than that associated with Humalog^® (mean VAS score of 24.2 mm, p=0.029 vs. Humalog^®).

Dr. Alan Krasner, Biodel’s chief medical officer, stated: “This study corroborates pharmacokinetic observations made previously in the diabetic swine model, namely that Biodel’s excipients accelerate the absorption of an insulin analog without prolonging the decline from peak concentration. This profile is different than that of the recombinant human insulin-based formulation BIOD-123, which is associated with a modestly longer decline from peak concentration compared to Humalog^®. The optimal decline from peak concentration for a prandial insulin is unknown and what is desirable may vary by patient.”

Errol De Souza, Biodel’s president and chief executive officer, stated: “The findings from these studies are very encouraging. Having established the proof of principle in man, we are now focused on replicating the pharmacokinetic and tolerability profiles of BIOD-250 in formulations utilizing lispro, the active pharmaceutical ingredient in Humalog^®, and in achieving commercial stability. We are pleased to have confirmed that we have a tolerability profile equivalent to currently marketed products, as previously seen in our Phase 1 trial of the recombinant human insulin-based ultra-rapid-acting candidate BIOD-123. BIOD-123 is now in a Phase 2 clinical trial scheduled to generate top line data in the third calendar quarter of 2013.”

Pharmacokinetic Profiles of BIOD-238, BIOD-250 and Humalog®
	Variable	BIOD-238 N=10	BIOD-250 N=11	Humalog® N=10	P-value BIOD-238 vs. Humalog®	P-value BIOD-250 vs. Humalog®
	Early ½ Tmax (minutes)	13.7 ± 1.9 (13.6)	14.6 ± 1.9 (12.9)	24.8 ± 2.9 (22.6)	<0.001	0.001
Absorption	Tmax (minutes)	35.5 ± 2.5 (37.5)	40.9 ± 6.1 (40.0)	62.5 ± 8.4 (60.0)	0.013	0.025
	AUCins0-30 (mU*min/L)	1278 ± 164 (1105)	1186 ± 133 (1260)	598 ± 126 (654)	<0.001	0.002
	AUCins0-45 (mU*min/L)	2421 ± 245 (2132)	2160 ± 195 (2327)	1486 ± 216 (1458)	<0.001	0.01
	AUCins0-60 (mU*min/L)	3476 ± 326 (3197)	3081 ± 245 (3125)	2505 ± 280 (2358)	0.002	0.066
Decline from peak concentration	Late ½ Tmax (minutes)	123.8 ± 10.5 (125.3)	132.3 ± 18.7 (117.0)	166.5 ± 10.6 (183.4)	0.009	0.016
Data represent the Mean ± SEM; Median Values are presented in parentheses.

Injection Site Toleration Profiles of BIOD-238, BIOD-250 and Humalog®
Metrics	BIOD-238 N=10	BIOD-250 N=11	Humalog® N=10
Tolerability (VAS 0 – 100 mm)	24.2 ± 7.0* (15.0)	2.7 ± 1.6 (0.0)	8.2 ± 4.5 (2.0)
Absolute Severity Score	1.09 ± 0.2* (1.0)	0.1 ± 0.1 (0.0)	0.5 ± 0.2 (0.0)
Relative Severity Score	3.6 ± 0.03 (4.0)	2.9 ± 0.02 (3.0)	3.2 ± 0.1 (3.0)
— Data represent the Mean ± SEM; Median Values are presented in parentheses.
— 100 mm Visual Analog Scale (VAS): 0 = no discomfort, 100 = worst possible discomfort
— Absolute Severity Scale: 0 = None, 1= Mild, 2 = Moderate, 3 = Severe
— Relative Severity (compared to usual meal-time insulin injections): 1 = Much less, 2 = Less,
3 = Equal, 4 = Increased, 5 = Greatly increased
— * p<0.05 vs. Humalog®

About Biodel Inc.

Biodel Inc. is a specialty biopharmaceutical company focused on the development and commercialization of innovative treatments for diabetes that may be safer, more effective and more convenient for patients. We develop our product candidates by applying our proprietary formulation technologies to existing drugs in order to improve their therapeutic profiles.

Safe-Harbor Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements about future activities related to the clinical development plans for the company’s drug candidates, including the potential timing, design and outcomes of clinical trials; and the company’s ability to develop and commercialize product candidates. Forward-looking statements represent our management’s judgment regarding future events. All statements, other than statements of historical facts, including statements regarding our strategy, future operations, future clinical trial results, future financial position, future revenues, projected costs, prospects, plans and objectives of management are forward-looking statements. The words “anticipates,” “believes,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The company’s forward-looking statements are subject to a number of known and unknown risks and uncertainties that could cause actual results, performance or achievements to differ materially from those described or implied in the forward-looking statements, including, but not limited to, the success of our product candidates, particularly our proprietary formulations of injectable insulin that are designed to be absorbed more rapidly than the “rapid-acting” mealtime insulin analogs presently used to treat patients with Type 1 and Type 2 diabetes and our liquid glucagon formulation that is intended to treat patients experiencing severe hypoglycemia; our ability to successfully complete a Phase 2 clinical trial of a proprietary insulin formulation in a timely manner, and the outcome of that trial; our ability to conduct pivotal clinical trials, other tests or analyses required by the U.S. Food and Drug Administration, or FDA, to secure approval to commercialize a proprietary formulation of injectable insulin or a liquid formulation of glucagon; the success of our formulation development work with insulin analog-based formulations of a proprietary injectable insulin and a liquid formulation of glucagon; our ability to secure approval from the FDA for our product candidates under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act; the progress, timing or success of our research, development and clinical programs, including any resulting data analyses; our ability to develop and commercialize a proprietary formulation of injectable insulin that may be associated with less injection site discomfort than Linjeta™ (formerly referred to as VIAject^®), which is the subject of a complete response letter we received from the FDA; our ability to enter into collaboration arrangements for the commercialization of our product candidates and the success or failure of any such collaborations into which we enter, or our ability to commercialize our product candidates ourselves; our ability to protect our intellectual property and operate our business without infringing upon the intellectual property rights of others; the degree of clinical utility of our product candidates; the ability of our major suppliers to produce our products in our final dosage form; our commercialization, marketing and manufacturing capabilities and strategies; our ability to accurately estimate anticipated operating losses, future revenues, capital requirements and our needs for additional financing; and other factors identified in our most recent report on Form 10-K for the year ended September 30, 2012. The company disclaims any obligation to update any forward-looking statements as a result of events occurring after the date of this press release.