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Exhibit 10.33

TERMINATION AGREEMENT

        This Termination Agreement (the "Agreement") is made as of this 30th day
of January 2008 (the "Termination Date") by and between Daiichi Sankyo
Company, Ltd. ("Daiichi Sankyo"), a Japanese corporation having its principal
place of business at 5-1 Nihonbashi-Honcho, 3-chome, Chuo-ku, Tokyo 103-8426,
Japan, and Metabasis Therapeutics, Inc. ("Metabasis"), a Delaware corporation
having its principal place of business at 11119 North Torrey Pines Road, La
Jolla, California 92037. Capitalized terms used herein but not otherwise defined
in this Agreement shall have the meanings set forth in the Amended and Restated
Collaborative Research and Development and License Agreement between
Sankyo Co., Ltd. (which was merged with Daiichi Sankyo as of April 1, 2007) and
Metabasis, dated June 30, 1999 (the "License Agreement").

WITNESSETH:

        WHEREAS, Daiichi Sankyo and Metabasis entered into the License Agreement
pursuant to which the parties conducted a research program and Daiichi Sankyo
commenced clinical development on the Licensed Compound known as CS-917 and also
entered into the Exclusive Option Agreement, dated as of October 21, 2002 (the
"Option Agreement") pursuant to which the parties conducted additional
activities in the Field, which Option Agreement has expired; and

        WHEREAS, Daiichi Sankyo and Metabasis have mutually agreed to terminate
the License Agreement;

        NOW, THEREFORE, in consideration of the premises and the mutual
agreements, covenants, and conditions set forth in this Agreement and other good
and valuable consideration, the receipt and sufficiency of which are hereby
acknowledged, Daiichi Sankyo and Metabasis, intending to be legally bound,
hereby agree as follows:

1.     Termination of License Agreement.

                (a)   Daiichi Sankyo and Metabasis each agrees that the License
Agreement shall be terminated as of the Termination Date. Notwithstanding
anything to the contrary in the License Agreement, effective upon the
Termination Date, all rights and obligations of the parties under the License
Agreement shall terminate except as expressly set forth in this Termination
Agreement. All rights to all compounds discovered or generated in the course of
research and development activities conducted by the parties under the License
Agreement and/or the Option Agreement, including, without limitation, all
Compounds, shall revert to (i) Metabasis if such compounds were discovered or
generated by Metabasis or were licensed to Metabasis from a Third Party and
(ii) Daiichi Sankyo if such compounds were discovered or generated by Daiichi
Sankyo.

                (b)   MTI Inventions shall continue to be owned by Metabasis and
Sankyo Inventions shall continue to be owned by Daiichi Sankyo, except as
provided in Section 2(c).

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                (c)   Notwithstanding the termination of the License Agreement,
Daiichi Sankyo and Metabasis, as applicable, shall undertake the obligations as
set forth in Section 1(a) above and Sections 2 and 3 below.

2.    Outstanding Obligations with Respect to Daiichi Sankyo.    Daiichi Sankyo
and Metabasis each agrees and acknowledges that, as soon as practicable after
the Termination Date, with respect to Daiichi Sankyo:

                (a)   Daiichi Sankyo shall keep open and active the
Investigational New Drug Application filed with the Food and Drug Administration
("FDA") for the Licensed Compound, as well as any comparable application(s)
filed with any regulatory body in any other jurisdiction for the Licensed
Compound (the "Regulatory Filings") while the following actions described in
this Section 2(a) are taken. Daiichi Sankyo shall, promptly after its
finalization, deliver to Metabasis (i) the final study report for the clinical
study (CS-917-A-U205), and (ii) the final study reports for the clinical
pharmacology studies (U-111 Cimet/Quin; U-113 BA-abbreviated CTR; and U112
14C/ADME). Daiichi Sankyo confirms that there are no final study reports with
respect to the Licensed Compound to be written other than those referenced in
the preceding sentence. Metabasis shall, within 90 days after receipt of all
such final study reports, notify Daiichi Sankyo in writing whether Metabasis
elects to have Daiichi Sankyo transfer the Regulatory Filings to Metabasis or to
have Daiichi Sankyo close the Regulatory Filings. Effective upon written notice
by Metabasis to Daiichi Sankyo that Metabasis elects to have Daiichi Sankyo
transfer the Regulatory Filings to Metabasis, Daiichi Sankyo shall, and hereby
does effective upon such written notice, transfer and assign the Regulatory
Filings to Metabasis so that Metabasis may conduct development activities with
the Licensed Compound pursuant to such Regulatory Filings. Daiichi Sankyo shall
also promptly transfer to Metabasis all documentation with respect to the
Regulatory Filings and shall make such filings with the FDA and any other
applicable regulatory body as necessary or appropriate to effect such transfer
and assignment to Metabasis. Daiichi Sankyo will bear any costs with respect to
such transfer and assignment to Metabasis and related filings. If Metabasis
elects to have Daiichi Sankyo close the Regulatory Filings or does not notify
Daiichi Sankyo in writing within such time frame, then Daiichi Sankyo shall
promptly take all necessary actions to close the Regulatory Filings.

                (b)   Daiichi Sankyo shall, and hereby does, transfer and assign
all data in the Regulatory Filings and all information and data from any
clinical or preclinical studies of the Licensed Compound conducted by or on
behalf of Daiichi Sankyo, including statistical models, integrated and
individual data sets, final reports and all regulatory correspondence, to
Metabasis, which information and data Metabasis may use for research,
development and commercialization of the Licensed Compound and any product
containing the Licensed Compound by or on behalf of Metabasis, including through
any affiliate, licensee or assignee. Daiichi Sankyo shall also promptly transfer
to Metabasis, at Daiichi Sankyo's expense, all documentation with respect to
such information and data. Daiichi Sankyo shall provide such data and Regulatory
Filings to Metabasis in electronic format.

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                (c)   Daiichi Sankyo shall, and hereby does, assign its interest
in (i) patent application No. MTI037 and (ii) the Sankyo Invention patent
applications numbered FP0529, and FP0626 (collectively, the "Patent
Applications", as more fully described in Exhibit A-1 attached hereto) to
Metabasis, and Metabasis shall thereafter bear all responsibility, expenses and
costs relating to such Patent Applications; provided, however, and subject to,
Metabasis granting to Daiichi Sankyo a non-exclusive, fully paid-up, perpetual,
irrevocable, worldwide license, including the right to grant sublicenses, to the
Patent Applications. Daiichi Sankyo shall promptly transfer to Metabasis all
documentation with respect to the Patent Applications, including, without
limitation, all correspondence with any patent office, and shall make such
filings with each applicable patent office as necessary or appropriate to effect
the assignment of the Patent Applications to Metabasis. Daiichi Sankyo will bear
any costs with respect to such transfer and assignment to Metabasis of the
Patent Applications and related filings. Daiichi Sankyo confirms to Metabasis
that Daiichi Sankyo does not own or control any patent, patent application or
invention with respect to compounds discovered, generated or developed in the
course of research and development activities conducted by the parties under the
License Agreement or the Option Agreement other than the Patent Applications.
Daiichi Sankyo shall abandon the Daiichi Sankyo Invention patent applications
numbered FP0318, FP0530, FP0706, FP0603 and JP2006-251995 (collectively, the
"Abandoned Applications", as more fully described in Exhibit A-2 attached
hereto) and shall not, whether directly or indirectly, revive or seek to revive
all or any part of the Abandoned Applications.

                (d)   Daiichi Sankyo confirms to Metabasis that Daiichi Sankyo
has ceased, in accordance with the agreement between Metabasis and Daiichi
Sankyo, all activities related to the toxicology, chemistry manufacturing and
controls, and pharmacokinetic studies and activities relating to the Licensed
Compound set forth in Exhibit B attached hereto, and shall not use any
materials, data or information from such activities, provided that Daiichi
Sankyo shall, at Daiichi Sankyo's cost, transfer 3 kg from the inventory of API
described in Exhibit B to Metabasis.

                (e)   Daiichi Sankyo shall remain responsible for all liability,
obligations, costs and expenses related to all studies and activities relating
to the Licensed Compound conducted by or on behalf of Daiichi Sankyo, including,
without limitation, those studies and activities set forth in Exhibit B, and
shall indemnify and hold harmless Metabasis and its directors and employees with
respect to any claims or losses arising from or relating to any such studies and
activities, except to the extent that any claims or losses are based solely upon
studies and activities for which Metabasis has an indemnification obligation
under Section 3(b).

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                (f)    Daiichi Sankyo shall destroy all FBPase constructs and
related expression vectors and protocols for screening and shall confirm in
writing to Metabasis that all of such items have been destroyed.

                (g)   Daiichi Sankyo shall, at Daiichi Sankyo's expense, store
blood samples obtained in connection with studies of the Licensed Compound and
shall not use such blood samples unless subsequently agreed in writing by
Daiichi Sankyo and Metabasis for potential future pharmacogenomic studies.
Should Daiichi Sankyo and Metabasis not agree on the pharmacogenomic studies,
Daiichi Sankyo may destroy such blood samples.

        (h)   Daiichi Sankyo may publish information from non-clinical studies
of the Licensed Compound as summarized on Exhibit C subject to compliance with
the conditions of this Section 2(h). Before any such material is submitted for
publication, Daiichi Sankyo shall first deliver a complete copy of the proposed
publication to Metabasis at least 30 days prior to submitting the material to a
publisher and obtain Metabasis' written consent to proceed with such
publication, provided that Metabasis shall notify Daiichi Sankyo of any comments
it may have within 20 days from the date which it receives such proposed
publication from Daiichi Sankyo and shall not unreasonably withhold such
consent.

3.     Outstanding Obligations with Respect to Metabasis.

                (a)   Daiichi Sankyo and Metabasis each agrees and acknowledges
that, as soon as practicable after the Effective Date, with respect to
Metabasis, Metabasis shall (i) accept assignment and assume full title and
ownership of the Patent Applications and (ii) grant to Daiichi Sankyo a
non-exclusive, fully paid-up, perpetual, irrevocable, worldwide license,
including the right to grant sublicenses, to the Patent Applications.

                (b)   Metabasis shall indemnify and hold harmless Daiichi Sankyo
and its directors and employees with respect to any claims or losses arising
from or relating to any future studies or activities conducted by Metabasis in
connection with, or relating to, the Licensed Compound, except to the extent
that any claims or losses are based solely upon studies and activities for which
Daiichi Sankyo has an indemnification obligation under Section 2(e).

4.    Indemnification Procedure.    A party entitled to indemnification pursuant
to Sections 2(e) or 3 (b) shall notify the indemnifying party promptly of any
claim that might give rise to a claim of indemnification, shall allow the
indemnifying party to handle the defense of the claim (provided the indemnifying
party acknowledges its obligation to indemnify hereunder), shall cooperate in
the defense of such claim, and shall not settle such claim without the
indemnifying party's written consent (which shall not be unreasonably withheld,
delayed or conditioned). An indemnified party shall have the right to
participate in the defense of any matter as to which indemnification is being
provided with its own counsel and at its own expense.

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5.    Release.    In consideration of the foregoing agreements, acknowledgments
and obligations, except as expressly set forth in this Agreement, Daiichi Sankyo
and Metabasis each agree that the other shall no longer bear any liability,
duty, or obligation whatsoever arising under or related to the License Agreement
or any matters relating to the relationship between the parties with respect to
research and development of compounds and products, including Compounds, for
treatment of diabetes, and shall be immediately released from any and all such
liabilities, duties or obligations arising prior to, and existing at, the time
of this Agreement. Each party acknowledges that it has read and understood
Section 1542 of the Civil Code of the State of California (set forth below) and
hereby expressly waives and relinquishes all rights and benefits under
Section 1542 and any law or legal principle of similar effect in any
jurisdiction with respect to the release set forth in this Section 5:

A general release does not extend to claims which the creditor does not know or
suspect to exist in his favor at the time of executing the release, which if
known by him must have materially affected his settlement with the debtor.

6.    Survival.    The provisions of Article 11 (Confidentiality) shall survive
termination of the License Agreement; provided that the parties acknowledge and
agree that all Information transferred or assigned to Metabasis pursuant to this
Agreement shall be Information of Metabasis.

7.    Notices.    All notices required or permitted under this Agreement shall
be in writing and shall be deemed to have been duly given when: (i) delivered by
hand, courier, or express mail service (with written confirmation of receipt);
(ii) sent by means of facsimile or other wire transmission (with provision for
assurance of receipt in a manner typical with respect to communications of that
type); or (iii) mailed by registered or certified first class mail, return
receipt requested, to the address or facsimile (fax) number set forth below (or
to such other person, address, or facsimile (fax) number as a party may, from
time to time, designate by written notice):

(i)if to Daiichi Sankyo:

Daiichi Sankyo, Company, Ltd.
2-58, Hiromachi 1 chome
Shinagawa-ku, Tokyo 140-8710
Japan
Attention: General Manager, Global Project Management,
                   R&D Division
Fax: 81-3-5740-3602

Vice President, General Counsel and Secretary
Daiichi Sankyo, Inc.
Two Hilton Court
Parsippany, NJ 07054
Fax: 973-630-2808

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(ii)if to Metabasis:

Metabasis Therapeutics, Inc.
11119 North Torrey Pines Road
La Jolla, California 92037
Attention: President and Chief Executive Officer
Fax: 858-458-3504

With a copy to:

Cooley Godward Kronish LLP
4401 Eastgate Mall
San Diego, California 92121
Attention: Kay Chandler
Fax: 858-550-6420

8.    Publicity.    A party shall not, except with the prior written consent of
the other party, issue, or cause to be issued, any press release, or other
public statement on or in any way related to this Agreement or the License
Agreement or the rights and obligations thereunder; provided, however, that
either party may (i) issue statements as required by applicable law and
(ii) disclose information or issue public statements already approved by a party
pursuant to the License Agreement, or with the prior consent of the other party.

9.    Governing Law.    This Agreement, including, without limitation, its
construction, interpretation, breach, and damages for breach, shall be governed
by and construed in accordance with the laws of the State of California (without
regard to its conflict of laws principles).

10.    Waiver.    A party's failure to exercise or enforce any right conferred
upon it hereunder shall not be deemed a waiver of any such right or any other
right or operate to bar the exercise or enforcement thereof at any time or times
thereafter; nor shall a party's waiver of any right hereunder at any time be
deemed a waiver thereof for any other time.

11.    Severability.    If any provision of this Agreement should be finally
determined by a court of competent jurisdiction to be invalid, illegal or
unenforceable for any reason, the parties shall negotiate in good faith a valid,
legal and enforceable substitute provision that most nearly reflects the
original intent of the parties and all other provisions hereof shall remain in
full force and effect in such jurisdiction and shall be liberally construed in
order to carry out the intentions of the parties as nearly as may be possible.
Such invalidity, illegality or unenforceability shall not affect the validity,
legality or enforceability of such provision in any other jurisdiction.

12.    Further Assurances.    Each of the parties shall perform such acts,
execute and deliver such instruments and documents, and do all such other things
as may be reasonably necessary to accomplish the purpose and transfer the
intellectual property rights, filings, data and activities contemplated under
this Agreement.

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13.    Counterparts, Headings and Ambiguities.    The division of this Agreement
into sections and the insertion of headings are for convenience of reference
only and shall not affect the construction or interpretation of this Agreement.
This Agreement may be executed in any number of counterparts, each of which
shall be deemed an original but all of which taken together shall constitute one
and the same instrument. In interpreting any provision of this Agreement, no
weight shall be given to, nor shall any construction or interpretation be
influenced by, the fact that counsel for one of the parties drafted this
Agreement, each party recognizing that it and its counsel have had an
opportunity to review this Agreement and have contributed to the final form of
the same.

14.    Entire Agreement.    This Agreement represents and contains the full and
complete understanding and agreement of the parties with respect to the subject
matter hereof and supersedes all prior and contemporaneous agreements,
understandings, statements, clauses, and conditions with respect to the
transactions contemplated by this Agreement or which may be contained in any
other form or document.

IN WITNESS WHEREOF, the parties have executed this Agreement as of the date
first above written.

DAIICHI SANKYO COMPANY, LTD.
 
METABASIS THERAPEUTICS, INC.
By:    /s/ Kazunori Hirokawa

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By:    /s/ Ed Baracchini

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Name:    Kazunori Hirokawa

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Name:    Ed Baracchini

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Title:    Executive Officer, Head of R&D Division

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Title:    SVP, Business Development

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Date:    Jan 30, 2008

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Date:    Jan. 31, 2008

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EXHIBIT A-1

PATENT APPLICATIONS

MT1037

Title:    Combination of FBPase Inhibitor and anti diabetic agents

<Combination use> FBPase inhibitors + Anti-diabetics (Insulin, SU etc.)

country

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  application No.

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  filing date

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AU   2001273271   7/5/2001     BR   P10112212-6   7/5/2001     CA   2412142  
7/5/2001     CN   1814924.3   7/5/2001     CZ   PV2003-5   7/5/2001     EP  
1952530.2   7/5/2001     HK             HU   US01/21557   7/5/2001     ID  
2002000977   7/5/2001     IL   153513   7/5/2001     IN   PCT/200201873  
7/5/2001     JP   2002-508433   7/5/2001     KR   2003-7000126   7/5/2001     MX
  PA/a/2002/012713   7/5/2001     NO   2003-0034   7/5/2001     NZ   523227  
7/5/2001     PL   365779   7/5/2001     RU   2003 7000126   7/5/2001     SG  
200207558-8   7/5/2001     SK   PP6-2003   7/5/2001     US   09/900364  
7/5/2001     VN   1-2003-00101   7/5/2001     WO   PCT/US2001/021557   7/5/2001
    ZA   2003/0044   7/5/2001    

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FP0529

Title:    Medicinal composition for treating diabetes

<Combination use> FBPase inhibitors + Biguanides

country

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  application No.

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  filing date

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BR   PI0519006-1   12/12/2005     CA   2590883   12/12/2005     CN      
12/12/2005     EP   5814764.6   12/12/2005     JP   2005-357073   12/12/2005    
KR   2007-7013097   12/12/2005     TW   94143827   12/12/2005     US   11/792879
  12/12/2005     WO   PCT/US2005/022739   12/12/2005    

FP0626

Title:    Drug containing FBPase Inhibitor

<Combination use> CS-917 + MK0431 (DPP-IV inhibitor)

country

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  application No.

--------------------------------------------------------------------------------

  filing date

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TW   95130334   8/18/2006     WO   PCT/JP2006/316292   8/21/2006    

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EXHIBIT A-2

ABANDONED APPLICAT1ONS

FP0318

Title:    Preventive agents for diabetes mellitus

<Use> treatment for IGT

country

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  application No.

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  filing date

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EP   3765368   7/23/2003     JP   2003-200333   7/23/2003     US   10/522401  
7/23/2003     WO   PCT/JP03/09348   7/23/2003    

FP0530

Title:    Medicinal composition containing FBPase Inhibitor

<Combination use> FBPase inhibitors + CS-011

country

--------------------------------------------------------------------------------

  application No.

--------------------------------------------------------------------------------

  filing date

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BR   PI0519015-0   12/14/2005     CA   2591416   12/14/2005     CN      
12/14/2005     EP   5816808.9   12/14/2005     JP   2005-359751   12/14/2005    
KR   2007-7013335   12/14/2005     TW   94144174   12/14/2005     US   11/818534
  12/14/2005     WO   PCT/US2005/022915   12/14/2005    

10

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FP0706

Title:    Preparation produced by dry process

<Formulation> process for preparing CS-917 tablet

country

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  application No.

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  filing date

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TW   96112406   4/10/2007     WO   PCT/JP2007/057832   4/9/2007    

Back-ups

FP0603

Title:    Thiazole compound

country

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  application No.

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  filing date

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JP   2006-82453   3/24/2006     WO   PCT/JP2006/305940   3/24/2006    

JP2006-251995

Title:    Pharmaceutical composition containing thiazole compound

country

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  application No.

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  filing date

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JP   2006-251995   9/19/2006    

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EXHIBIT B

ONGOING STUDIES AND ACTIVITIES RELATED TO THE LICENSED COMPOUND

TOX

Mouse CA study   -Start of administration: May 24, 2006   -Facility BOZO
research (CRO, Japan)
Rat CA study
 
-Start of Administration: June 13, 2006
 
-Facility: BOZO research (CRO, Japan)
 
 
 
 
 

CMC

Inventory of API (final method) in GMP condition   About 300kg   To be retested
Inventory of clinical supply in GMP condition
 
25mg 550K tabs, 50 mg 550K tabs, 100mg 500K tabs and placebo 1.2M tabs
 
Use by date
-Placebo: Sep 2011
-25mg, 50mg, 100mg: Oct 2010
Stability studies (API, DP)
 
DP: Planned for 3 years (Oct 2006-Oct 2009)
 
 
DMF
 
Annual report was submitted in July 2007
 
 

 

 

 

 

 

PK

Measurement of PK sample in the 205 study   Preliminary measure was completed  
-Facility: Simbec, UK

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EXHIBIT C

PUBLICATION PLAN RELATED TO NON-CLINICAL STUDIES OF CS-917 AND BACKUP COMPOUNDS

TOX

Area

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  Title (tentative)

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  Timing for submission

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Pharmacology   CS-917 inhibits hepatic GNG In vivo and improves post prandial
hyperglycaemia in GK rats   1Q 2008
Pharmacology
 
CS-917 decreases PG and acts on liver as prodrug in cynomolgus monkeys
 
1Q 2008
Pharmacology
 
CS-917 decreases hepatic glucose production, whereas metformin increases
intestinal lactate production
 
1Q 2008
Pharmacology
 
Different effects of CS-917 and metformin in vivo and possibility of combination
treatment
 
2Q 2008
Pharmacology
 
Enhancement of Insulin action improves lactate metabolism in combination with
CS-917
 
3Q 2008
ADME
 
Preclinical Pharmacokinetics and ADME of CS-917
 
by the end of 2009
ADME
 
Identification of renal transporters in human
 
by the end of 2009
ADME
 
Identification of activating enzymes in human
 
by the end of 2009
ADAM
 
Species differences, including human, in hepatic uptake
 
by the end of 2009
ADME
 
Species differences, including human, in renal excretion
 
by the end of 2009
ADME
 
Human Metabolism
 
by the end of 2009
Analysis
 
Elucidation of the chemical structure of volatile degradation product and their
degradation mechanism for active pharmaceutical ingredients
 
4Q 2008
Process research
 
Development of manufacturing process for CS-917
 
by the end of 2009
Back up compounds (Medicinal chemistry)
 
Novel tricyclic derivatives as potent FBPase inhibitors (several articles*)
 
by the end of 2009
 
 
 
 
 

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*The number of articles has not fixed yet.

All articles are subject to review by Metabasis before submission.

Daiichi Sankyo will not newly initiate studies related to those listed in this
table.

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QuickLinks

Exhibit 10.33

TERMINATION AGREEMENT
EXHIBIT A-1 PATENT APPLICATIONS
EXHIBIT A-2 ABANDONED APPLICAT1ONS
EXHIBIT B ONGOING STUDIES AND ACTIVITIES RELATED TO THE LICENSED COMPOUND
EXHIBIT C PUBLICATION PLAN RELATED TO NON-CLINICAL STUDIES OF CS-917 AND BACKUP
COMPOUNDS