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Exhibit 10.21    
    

***Text Omitted and Filed Separately

Pursuant to a Confidential Treatment Request

Under C.F.R. §§ 200.80(b)(4) and Rule 406

of the Securities Act of 1933, as amended.  

	[LOGO]	 	12651 High Bluff Dr., Ste. 200

San Diego, CA 92130

P: (858) 509-0455 F: (858) 509-0456	 	PO #:

Date:	 	MFG 065

02/16/07

PURCHASE ORDER         

	Vendor Info.
	 	Ship To:

	Name	 	Patheon Italia S.p.A.	 	Name	 	Mark Mugerditchian
	Address	 	Viale G.B. Stucchi, 110	 	Address	 	12651 High Bluff Drive Suite 200
	City	 	Monza	 	State	 	Italy	 	Zip	 	20052	 	City	 	San Diego	 	State	 	CA	 	Zip	 	92130
	Ph/Fax:	 	919-479-8850	 	Ph/Fax:	 	858-523-4506

	Qty
	 	Units
	 	Description
	 	Unit Price
	 	Total

	 	 	 	 	Contract Manufacturing and Supply of KW-3902 iv sterile emulsion to include the production of [. . .***. . .] registration stability batches and [. . .***. . .] process validation
batches according to the attached proposal Rev 3 - 16.02.2007	 	 	 	-

-

-

-

-

-
	 	 	 	 	The Proposal includes the following breakout of charges:	 	 	 	-
	1.0	 	 	 	Development and Manufacturing	 	[. . .***. . .]	 	[. . .***. . .]
	1.0	 	 	 	Capital Equipment and Facility Modifications	 	[. . .***. . .]	 	[. . .***. . .]

-
	 	 	 	 	 	 	 	 	-

-
	 	 	 	 	 	 	 	 	

	 	 	 	 	 	 	Sub Total	 	[. . .***. . .]
	Date Required:	 	Nov-07	 	S&H	 	 
	Est. Delivery Date:	 	Taxes:	 	State 0.00%	 	-
	 	 	 	 	 	 	 	 	

	Dept & Acct to Charge:	 	 	 	TOTAL	 	€[. . .***. . .]
	 	 	 	 	 	 	 	 	

Approvals:  

	

/s/ Mark Mugerditchian 2/16/07
 Department Head / Date	
 	

/s/ R.E. Woods 16 Feb 07
 Pres & CEO / Date

	Notes / Comments	 	 
	 	 	

	 	 	

	 	 	

***Confidential Treatment Requested

Confidential

Page 1 

	[LOGO]	 	KW-3902 i.v. — Transfer & commercial

manufacture proposal for NovaCardia.

Rev 3—16.02.2007

16th February 2007  

NovaCardia  

Attention:    Mark Mugerditchian—SVP Manufacturing and Product Development 

Dear
Mark, 

Ref: Contract Manufacture and Supply of KW-3902 i.v. Sterile Emulsion.  

Based on various discussions between the two parties, I am happy to provide a final proposal which I hope meets with your requirements and expectations. 

You
will notice below that we have [. . .***. . .] 

This
proposal has been made in good faith based upon the product information received to date and is subject to review following receipt and further discussions of the updated / out of scope detailed
transfer and manufacturing requirements between the parties. The assumptions we have made in generating this proposal are listed in the body of this letter. 

I
trust that the enclosed information is in an acceptable format, but should anything be unclear or you have any further questions please do not hesitate to contact me. 

Please
let me have your confirmation of acceptance of this proposal in the form a purchase order for capital and technical transfer costs to allow us to move the project forward. 

Warm
regards 

[. . .***. . .]

Senior Business Manager—Ferentino Operations.

Cc.
[. . .***. . .] 

***Confidential Treatment Requested

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Page 2 

Index  

	1)
	Project brief.

	2)
	Key product parameter overview

	3)
	Key manufacturing supply assumption

	4)
	Product Technology Transfer (TT)

	5)
	Technology Transfer (TT) costing estimates

	6)
	Regulatory support work

	7)
	Stability Testing Programme.

	8)
	Annual Product Review (APR)

	9)
	CapEx proposal and costing

	10)
	Unit pricing indication

	11)
	General Terms and Conditions  

Confidential

Page 3 

1.    Project Brief    

KW-3902
i.v., ([. . .***. . .]) is a synthesized adenosine A1-receptor antagonist. The compound is
highly useful as a diuretic, hypotensive and renoprotective agent. The manufacturing process consists of five (5) stages: API Solution Preparation, Rough Emulsion, Fine Emulsion, Filling and
Inspection/Packaging. 

NovoCardia
are looking for commerical supply of KW-3902 i.v. for the US and RoW markets. Current scale-up and demand volumes are as follows: 

	[. . .***. . .]:	 	[. . .***. . .] Registration / Stability batches
	[. . .***. . .]:	 	[. . .***. . .] × full scale validation batches
	[. . .***. . .]:	 	Launch of product
	[. . .***. . .]:	 	[. . .***. . .] vials
	[. . .***. . .]:	 	[. . .***. . .] vials
	[. . .***. . .]:	 	[. . .***. . .] vials
	[. . .***. . .]:	 	[. . .***. . .] vials

2.    Key Product Parameter Overview:    

	Product	 	KW-3902 i.v. [. . .***. . .]mg/mL vials
	Dosage form	 	Sterile Emulsion
	Vial size	 	[. . .***. . .]mL (overflow capacity)
	Fill Volume	 	60mL ([. . .***. . .]mg / mL)
	Batch size	 	[. . .***. . .] vials (Assumes [. . .***. . .]L batch size)
	Annual Volumes	 	See above.

3.    Key Manufacturing Supply Assumptions:    

Health and Safety evaluation—a preliminary EH&S toxicity classification of the API has been performed by Patheon. It has been determined
that the API molecule is [. . .***. . .]. 

Our
categorisations work on a scale of 1-4, 4 being the most potent. Please note that each and every molecule and product must be assessed on its own merits taking into account the
required handling and processing requirements based on the molecule occupational exposure level (OEL). Needless to say operator and environmental safety are paramount and Patheon will not take on
products that it can not manage in a safe and secure way. 

[. . .***. . .]
products present no issue from a EH&S perspective. 

***Confidential Treatment Requested

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Page 4 

Target Production Site—The target site for the transfer, validation and commercial production of the KW-3902 i.v. will be the
[. . .***. . .] at the Ferentino site near Rome, Italy. 

The
Ferentino site is FDA product approved, and listed below is a chronological summary of regulatory site inspections for reference. The
[. . .***. . .] is FDA approved for commercial manufacture. 

FERENTINO—Patheon Italia S.p.A.—Ferentino Operations—Regulatory Inspection List  

Inspectorate
Body: Italian Ministry of Health

Date of the Inspection: [. . .***. . .]

Scope of the Inspection: Extension of [. . .***. . .] to include
[. . .***. . .]. 

Inspectorate
Body: Italian Ministry of Health

Date of the Inspection: [. . .***. . .]

Scope of the Inspection: [. . .***. . .] for manufacturing of
[. . .***. . .]. 

Inspectorate Body: US Food and Drug Administration (FDA)

Date of the Inspection: [. . .***. . .]

Scope of the Inspection: [. . .***. . .] for manufacturing of
[. . .***. . .].

Inspectorate
Body: Italian Ministry of Health

Date of the Inspection: [. . .***. . .]

Scope of the Inspection: Extension of [. . .***. . .] to include
[. . .***. . .]. 

Inspectorate
Body: Italian Ministry of Health

Date of the Inspection: [. . .***. . .]

Scope of the Inspection: [. . .***. . .] for
[. . .***. . .]. 

Batch size—Patheon has assumed a batch size of [. . .***. . .]L.
Based on discussion Patheon will move forward with the [. . .***. . .]L
batch size with the provision that the necessary investments will be made by NovaCardia to scale up to a [. . .***. . .]L
batch size for commercial production. All necessary investments will be discussed, determined and agreed between both parties. 

API—it has been assumed that NovaCardia will provide the API free issue to Patheon, which will be released and will require only an i.d.
test. 

API
and Finished Product shipment and storage conditions: Ambient Temperature. It is noted that [. . .***. . .] and
[. . .***. . .] must be stored at
[. . .***. . .]°C. 

***Confidential Treatment Requested

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Materials—Components and Excipients—Patheon will procure all components (vials, stoppers, caps) and excipients for the
commercial manufacture from Patheon qualified suppliers i.e. Patheon supplies everything excluding API. Should NovaCardia require Patheon to source any materials from NovaCardia specified suppliers
then these suppliers [. . .***. . .]. 

[. . .***. . .]  Sterilisation—[. . .***. . .] 

[. . .***. . .]
 Sterilisation—[. . .***. . .] 

[. . .***. . .]
 Validation—[. . .***. . .] 

[. . .***. . .]
 Validation—[. . .***. . .] 

Quality Control—IPC and FP to be tested in accordance with NovaCardia specifications. It has been assumed that the testing is to
standardised EP/USP requirements. Any client or product specific testing requirements would require a full assessment. 

Product Coding—Vials to be ink jetted with "Batch number and Expiry Date" on the cap collar. 

Visual Inspection—100% vial visual inspection to be performed by semi-automatic means with qualified operators. Defect
characteristics and AQL to be established and agreed. 

Primary Packaging—USP glass type I moulded vial—60mL
([. . .***. . .] vial to be approved) 

Secondary Packaging—It is understood that NovaCardia require secondary packaging. Patheon must review/analyse the packaging specifications
requirements upon receipt from NovaCardia in order to align capabilities and provide a proposal. 

Process Flow Description—Patheon assumes the following production process shown on the following page, based on current information provided
by NovaCardia and discussions with Mova Colleagues. Patheon would like to utilise the current [. . .***. . .]L
tanks([. . .***. . .]) ([. . .***. . .]L batch
size) for the [. . .***. . .] and
[. . .***. . .] batches. 

***Confidential Treatment Requested

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First Step:  

[. . .***. . .] 

Second Step:  

[. . .***. . .]

***Confidential Treatment Requested

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Page 7 

4.    Product Technology Transfer (TT):    

The
Technology Transfer strategy of any product into Patheon must be made in conjunction with the client to ensure compliance with the Product Registration. 

As
a dedicated contract manufacturer of pharmaceutical products, product introduction and transfer into our facilities are a vital aspect of our routine business. Patheon has dedicated Technology
Transfer groups at each site who are fully focused on the co-ordination and project management for such transfers. Below is an outline of some of the main activities that we would perform
for a typical sterile product transfer: 

	•
	Regulatory GAP Analysis and Document
Preparation—[. . .***. . .].

	•
	Media Fill Runs—[. . .***. . .].

	•
	Analytical Method
Transfers—[. . .***. . .]. 

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	•
	Equipment Qualification /
Validation—[. . .***. . .].

	•
	Engineering/placebo
batch—[. . .***. . .].

	•
	Cleaning validation—[. . .***. . .].

	•
	[. . .***. . .]
 Validation—[. . .***. . .] 

5.    Typical Technology Transfer (TT) Costing Estimates    

	Item (Tech transfer)
 
	 	#
	 	Cost (€)
	 	Total Cost (€)

	API Health & Safety Evaluation	 	N/A	 	N/A	 	N/A
	QA documentation review [. . .***. . .].	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	Analytical Method Transfer [. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]

***Confidential Treatment Requested

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	Sterility assurance / re-qualification work — [. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	Project controlling validation documentation — [. . .***. . .].	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	Media Fill Runs [. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	Dedicated equipment installation and qualification [. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .] Feasibility batches (full scale) — [. . .***. . .].	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .] Stability / Registration batches (full scale)	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	Cleaning process Validation — [. . .***. . .].	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]
	Business / Project Management ([. . .***. . .]% of TT cost)	 	[. . .***. . .]	 	 	 	[. . .***. . .]
	Total	 	 	 	 	 	€[. . .***. . .]

	•
	All
products produced from the validation batches are to be purchased by the client at the commercially agreed unit prices.

	•
	Technology Transfer cost is charged at [. . .***. . .] in the form of a
purchase order from Novocardia upon Patheon being awarded the project and then [. . .***. . .]% on
completion and submission to NovaCardia of the Process Validation Report and the batch certificates of analysis. 

	[. . .***. . .] Process Validation — [. . .***. . .].	 	[. . .***. . .]	 	[. . .***. . .]	 	[. . .***. . .]

6.    Regulatory Support work:    

Patheon
will help and support NovaCardia with their submissions to approve Patheon as a site of manufacture for the products. The scope and depth of regulatory support provided by Patheon can be
agreed upon depending on NovaCardia's needs. 

Regulatory
work will be charged at €[. . .***. . .]. 

***Confidential Treatment Requested

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Page 10 

7.    Stability Testing Programme:    

If
required, stability studies can be performed by Patheon. Patheon can store and test in accordance with an agreed protocol and ICH guidelines. For example: 

A
full ICH stability programme can be performed on each of the validation batches / registration batch, and a typical charge per sample time point is indicated below. This fee is to be confirmed upon
receipt of the full stability testing analysis required. 

Charge
per time point is €[. . .***. . .]. 

8.    Annual Product Review (APR)    

On
January 1, 2006, the most recent revision of Chapter 1 "Quality Management" in the EC GMP Guideline came into operation and introduced a new regulatory requirement: the Product Quality
Review (PQR). 

This
comprehensive evaluation, called also Annual Product Review (APR), should be conducted for all licensed medicinal products and include data
collection, trending and critical analysis of: 

	•
	Materials
and Components

	•
	Critical
IPC and finished product results.

	•
	Deviations,
OOS

	•
	Changes

	•
	Stability
studies

	•
	Complaints

	•
	Corrective/Preventive
Actions

	•
	Qualification/Validation

	•
	Technical
Agreements 

APR
work will be charged at €[. . .***. . .]. 

9.    Capital Equipment    

	Equipment
 
	 	Estimated Cost of

Equipment (Euro)

	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]

***Confidential Treatment Requested

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Page 11 

	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	TBD
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	[. . .***. . .]	 	[. . .***. . .]
	Total	 	€[. . .***. . .]

All
CapEx items will be agreed with NovaCardia against specific "User Requirements" and will be purchased by Patheon and then billed back to NovaCardia at  "[. . .***. . .]".[. . .***. . .]
. 

[. . .***. . .]

[. . .***. . .] by issuance of a purchase order to Patheon.
Only [. . .***. . .] against this purchase order. Supplier quotations /
invoices can be provided if / when necessary.

10.    Unit Pricing Indication    

	Batch size (L)
 
	 	Batch size (# vials)
	 	Unit price

(without materials cost)

	[. . .***. . .]L	 	[. . .***. . .]	 	€[. . .***. . .]
	[. . .***. . .]L	 	[. . .***. . .]	 	€[. . .***. . .]
	[. . .***. . .]L	 	[. . .***. . .]	 	€[. . .***. . .]

***Confidential Treatment Requested

Confidential

Page 12 

Note:  

	•
	[. . .***. . .]

	•
	[. . .***. . .] 

11.    General Terms and Conditions—    

The
following (not limited to) Terms and Conditions are applicable 

	•
	All
stated Values / Invoices are in (€) Euros.

	•
	Prices
will be fixed for the term of the agreement[. . .***. . .].

	•
	Product
Price is [. . .***. . .].

	•
	All
prices indicated exclude VAT.

	•
	Invoice
payment terms are [. . .***. . .] from date of invoice.

	•
	Capacity
is [. . .***. . .] basis. 

***Confidential Treatment Requested

Confidential

Page 13 

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Exhibit 10.22    
    

 
 

Description of Annual Executive Bonus Plan    
    

        The Compensation Committee (the "Committee") of the Board of Directors (the "Board") of NovaCardia, Inc. (the "Company") is responsible for setting annual
discretionary cash bonus compensation for the Company's executive officers. Near the beginning of each year, the Committee reviews a detailed set of overall corporate performance goals and
value-creating milestones for the current year prepared by management that are intended to apply to the executives' bonus awards and, with some distinctions, to the bonus awards for all of the
Company's other employees. The Committee works with management to develop final corporate performance goals that are set at a level that the Committee believes management can reasonably achieve with
hard work over the next year. The Committee has established target bonus awards of up to 25% of base salary for executives for 2007. The amount of actual bonuses paid to the Company's executives will
be determined by the Committee and the Board and paid at the end of 2007, or in early 2008, and may be above or below target bonus levels. 

        At
the end of each year, the Committee, determines the level of achievement for each corporate goal and value. Final determinations as to discretionary bonus levels are then based in
part on the achievement of these corporate goals or milestones, as well as the Committee's assessment as to the overall success of the Company and the development of its business. These corporate
goals and milestones, and the proportional emphasis placed on each goal and milestone may vary, from time to time, depending on the Company's overall strategic objectives, but relate generally to
factors such as achievement of clinical and regulatory milestones for product candidates, identifying and in-licensing new product candidates, establishment of collaborative arrangements
and to financial factors such as raising or preserving capital. 

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Exhibit 10.22

Description of Annual Executive Bonus Plan

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00120-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00120-of-00352.parquet"}]]